Pemphigus vulgaris: Retrospective analysis supports role of cyclophosphamide

Key Points

National report- Results of a retrospective study including long-term follow-up emphasize the importance of considering relapse risk when selecting therapeutic intervention for patients with moderate-to-severe pemphigus vulgaris.

Adjuvant therapy combination treatment with a corticosteroid with cyclophosphamide may offer benefits for providing safe, effective and durable disease control, according to Malgorzata Olszewska, M.D., Ph.D., assistant professor, department of dermatology, Warsaw Medical School, Poland, reporting the findings from an analysis of clinical relapse rates during a minimum follow-up of five years after treatment discontinuation for immunologically confirmed pemphigus vulgaris.

Study parameters

About half of the patients received prednisone plus cyclophosphamide, while the rest were nearly equally distributed among the three remaining treatment groups.

Relapses were common during follow-up, occurring in 44 percent of patients. However, there was wide variability in relapse rates and time to first relapse among the different treatment groups.

The best outcomes for both of those endpoints occurred among patients treated with prednisone and cyclophosphamide, Dr. Olszewska tells Dermatology Times.

Long-term efficacy

"Most studies of treatments for pemphigus vulgaris are short-term. However, evaluating medication efficacy based solely on the likelihood of inducing a clinical remission can be misleading ... Rather, the potential to provide long-term efficacy must also be considered as an important criterion for therapeutic selection," Dr. Olszewska says.

"Azathioprine is often used as a first-line adjuvant to corticosteroids to treat pemphigus vulgaris, based on the belief it is more effective and safer than cyclophosphamide.

"This retrospective analysis shows the proportion of patients who remain disease-free over the longer term is higher with use of prednisone plus low-dose cyclophosphamide," she says.

Dosing

Initial daily doses for the adjuvant medications were 100 mg for azathioprine and cyclophosphamide and 2.5 mg/kg to 3 mg/kg for cyclosporine.

All adjuvants were maintained at the same dose for at least six weeks, and then tapered based on response and leading to discontinuation at about three months after clinical remission.

The prednisone dose was also tapered and subsequently discontinued.

Results

Only 28 percent of patients treated with prednisone plus cyclophosphamide developed a relapse; mean time to first relapse was 27.4 months. Relapse rates in the other three treatment groups were nearly twofold greater or even higher (51 percent to 68 percent).

Compared with the prednisone plus cyclophosphamide group, mean time to first relapse was significantly shorter in patients treated with prednisone monotherapy (21 months) or with prednisone in combination with cyclosporine (11 months).

There was a trend for a significantly faster time to relapse in the patients who received the steroid plus azathioprine (25 months).

A safety review of adverse effects associated with the various treatment regimens showed no statistically significant differences between groups in overall rates or the incidence of adverse events leading to hospitalization.

"A handful of patients treated with cyclophosphamide developed hematuria, but it resolved when the drug was discontinued.

"With available follow-up ranging to 18 years, no patient has developed bladder cancer," Dr. Olszewska says.