Efficacy of Dapsone as a Steroid Sparing Agent in Pemphigus Vulgaris
Efficacy of Dapsone as a Steroid Sparing Agent in Pemphigus Vulgaris
The purpose of this 12-month study was to determine the efficacy of dapsone as a
 glucocorticoid-sparing agent in maintenance phase pemphigus vulgaris.
Patients were entered into the trial on steroids in combination with cytotoxic agents as
 needed. The steroid dose was the lowest dose at which the patient's disease was controlled
 before the last flare (see eligibility criteria). The patients were randomized to receive
 either Dapsone or placebo. Treatment was to be started at a dose of 50 mg and increased by 25
 mg increments each week once the hemoglobin was shown not to have dropped by more than 2
 gm/dl. The target dose was 150 mg and patients who did not respond could be advanced to 200
 mg daily. After beginning treatment, a standardized steroid taper was commenced. A
 standardized steroid taper was suggested with tapering by 10 mg/wk for doses above 40 mg/day
 or more slowly if warranted. A slower taper thereafter or an every other day dosing schedule
 would be elected according to the individual investigator's preference. Flares were treated
 by increasing the dose of steroids - in the case of a mild flare to the last dose preceding
 the flare, in the case of a moderate flare by 20 mg/day and in the case of a severe flare by
 40 mg/day. Tapering was to be resumed once the disease had stabilized. Disease activity was
 assessed by a simple scoring system for skin, mucosa, and sites involved. Laboratory
 assessments initially weekly became monthly once the study medication dosage was stabilized.
Inclusion Criteria:

 -  Histologic evidence compatible with pemphigus vulgaris and direct immunofluorescence
 evidence of pemphigus vulgaris.

 -  Chronic disease that has been controlled with steroids and/or cytotoxics, e.g.
 maintenance phase.

 -  On prednisone 15 or more mg/day to around 40 mg/day or on prednisone 15 or more mg
 every other day (qod) to around 40 mg qod.

 -  Failure to taper steroids below a range of 15 mg/day to around 40 mg/day or 15 mg/qod
 to around 40 qod without flaring the disease.

 -  The steroid dosage at which the most recent flare occurred should not be less than 85%
 of the last (within 30 days) dosage which controlled the disease, i.e. 85% of the
 baseline steroid dosage. This is to ensure that patients will not have had a recent
 acute flare at the time of entry into the study, and be in the rapid steroid taper
 portion of their disease after such a flare.

 -  Two baseline steroid dosages as determined by prior flares. It is common that patients
 will be repetitively unable to taper below a certain baseline steroid dose without
 experiencing a mild flare of their disease. This baseline dose will be determined on
 two occasions during attempted tapers, and the baseline number then averaged to
 determine the dose of steroid the patient is on at the time of entry into the study.

 -  No pulse steroids, pulse cyclosphosphamide, or plasmapheresis within two months of
 beginning the protocol. This will exclude patients who had recent acute flares of
 their disease and may be on the rapid steroid taper portion of their disease. The
 patient must be in maintenance phase, as defined in the criteria listed in e.

 -  Patient understands the procedures and agrees to participate in the study program by
 giving written informed consent.

 Exclusion Criteria:

 -  Patients able to taper steroids without recurrence of disease.

 -  Patients with early, severe disease that have not responded to high doses of
 prednisone, cytotoxics, plasmapheresis, or other modalities.

 -  Contraindications to the use of Dapsone, including severe anemia or G6PD deficiency.

 -  Patient has behavioral problems that might interfere with compliance.

 -  Pregnancy or breast-feeding.

 -  Younger than 18 or older than 80 years of age. Since PV is rare in patients younger
 than 18, it was decided to exclude this potentially different population. It is
 unlikely that this will exclude many patients. Dapsone induces a hemolytic anemia,
 which would be a particular problem for patients over age 80, who are more likely to
 have ischemic heart disease or other atherosclerotic vascular disease.

 -  History of allergy to dapsone.

 -  Ischemic heart disease