Kinetics of Response to Conventional Treatment in Patients With Pemphigus Vulgaris

It is difficult to evaluate the effectiveness of new therapies for pemphigus vulgaris (PV) because controlled trials are rarely performed. Comparison to historical trials is also problematic because little is known about the frequency and time it takes for active pemphigus to respond to conventional treatment.^1,2 To address this problem, we evaluated the kinetics of response in PV to conventional treatment with prednisone.

A retrospective study was conducted in 29 sequential patients with PV based on clinical, histological, and immunofluorescence criteria. All patients met the following inclusion criteria: (1) they had experienced a flare in disease activity (≥ 3 new lesions per week) while undergoing treatment with stable or tapering doses of prednisone; (2) they had been treated only with systemic steroids prior to the flare; and (3) the flare was treated only with prednisone. The median disease duration was 7 months (range, 2 months to 11 years). The median prednisone dose at the time of the flare was 2.5 mg/d (range, 0-32 mg/d). Patients were treated by increasing the dose of prednisone in steps of 10 to 20 mg/d every 1 to 2 weeks until disease activity was controlled (<1 new lesion per week). No adjuvant therapy was added. The dose that controlled disease activity was maintained until approximately 80% of the lesions were healed (end of consolidation phase), at which point the dose was gradually tapered, usually by 5 mg every 2 to 3 weeks.

The median time to control disease activity was 3 weeks (range, 1-17 weeks), and the median maximum dose of prednisone required was 40 mg/d (range, 5-90 mg/d) (Table 1). Disease activity was controlled 2 weeks after raising the prednisone dose in 41% of patients (n = 12) and after 3 weeks in 62% (n = 18) (data not shown). The end of the consolidation phase was reached after a median of 4 weeks from treatment of the flare (range, 1-17 weeks). The prednisone dose could be reduced by 50% of the maximum level required to control disease activity after a median of 7 weeks from the start of treatment (range, 1-30 weeks). After 4 months, 38% of patients achieved partial remission (no lesions for ≥1 month with <15 mg/d of prednisone) (n = 14); after 9 months, 62% (n = 18) (data not shown). Complete remission (no lesions for ≥1 month with no systemic treatment) was achieved in 24% of patients at 11 months (n = 7).

The prednisone dose required to control disease activity and the kinetics of response were related to the baseline dose of prednisone at the time the flare occurred (Table 2). A median maximum prednisone dose of 20 mg/d was required to control disease activity in patients whose disease flared while they were not undergoing treatment with systemic steroids, while 45 mg/d was required for those on a prednisone regimen of 10 mg/d or higher. At 11 months, complete remission was induced in 36% (n = 4) and 0% of the 2 groups, respectively. Patients who were not undergoing systemic therapy prior to a flare reached the end of the consolidation phase and had a 50% decrease in their maximum prednisone dose a median of 2 weeks earlier in each case than those on a prednisone regimen greater than 10 mg/d (data not shown). There was 1 grade 2 (localized infection) and no grade 3 toxic effects during this 11-month period.³

These results indicate that flares in the activity of pemphigus vulgaris respond rapidly to conventional treatment with systemic steroids. Flares in disease activity were controlled a median of 3 weeks after increasing the steroid dose. After a median of 4 weeks, the steroid dose began to be tapered, and after 7 weeks, the dose could be tapered to half the maximum dose.

The rate of complete remission was 24% at 11 months (n = 7). This is consistent with a prior study, which found that complete remission occurred in 25%, 50%, and 75% of patients at 2, 5, and 10 years, respectively, following diagnosis.¹ Partial remission was 76% at 11 months (n = 22), similar to a 71% remission rate after treatment with mycophenolate and prednisone after 13 months.⁴

Patients receiving a lower baseline dose of systemic steroids required less prednisone (lower maximum dose and increased rate of taper) and were more likely to achieve complete remission than those taking a higher baseline dose. These results suggest that the kinetics of response to treatment is related to the baseline dose of medication and that this variable needs to be considered when judging response to new therapies. Furthermore, these results provide a benchmark against which the results of newer therapies can be evaluated.

Correspondence: Dr Bystryn, New York University School of Medicine, 550 First Ave, Tisch Hospital, H313, New York, NY 10016 (bystryn@nyu.edu).

Author Contributions:Study concept and design: Czernik and Bystryn. Acquisition of data: Czernik. Analysis and interpretation of data: Czernik. Drafting of the manuscript: Czernik. Critical revision of the manuscript for important intellectual content: Czernik and Bystryn. Statistical analysis: Czernik. Administrative, technical, and material support: Czernik. Study supervision: Bystryn.

Financial Disclosure: None reported.

Funding/Support: This study was supported in part by US Food and Drug Administration grant 1R01FD-03343-01 (Dr Bystryn).

Additional Contributions: Albert Einstein College of Medicine provided assistance for this study.