Blistering Skin Disorders Evidence Based Update Pemphigus Trials

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Blistering Skin Disorders Evidence Based
UpdatePemphigus Trials

• Prof. Marcel F. Jonkman
• Centre for Blistering Diseases
• Groningen, the Netherlands
• Holywell Park, Loughborough 5 June 2008

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(No Transcript)
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Randomized non-blinded clinical trials in
pemphigus
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Chams-Davatchi et al. J Am Acad Dermatol
200757622-8
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Steroid pulse therapy in pemphigus

• Pasricha 1988 Br J Dermatol
• Kaur 1990 Int J Dermatol
• Pasricha 1992 Int J Dermatol
• Appelhans 1993 Hautarzt
• Pasricha 1995 Int J Dermatol
• Chryssomallis 1995 Int J Dermatol
• Pasricha 1996 Arch Dermatol
• Werth 1996 Arch Dermatol
• Tóth 2002 J Eur Acad Dermatol Venereol
• Kanwar 2002 Dermatology
• Mignogna 2002 J Oral Pathol
• Femanio 2002 J Eur Acad Dermatol Venereol
• Sacchidanand 2003 Dermatol Online J
• Jain 2003 J Dermatol
• Mahajan 2004 Int Dermatol
• Jain 2005 Int J Dermatol
• Rose 2005 J Deutsche Dermatologische Gesellschaft
• Mentink 2006 Arch Dermatol

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Randomized placebo-controlled trials in pemphigus
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Mentink et al. Arch Dermatol 2006
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PEMPULS trialInternational Randomised Controlled
Trial of Steroid Pulse Therapy in Pemphigus
Vulgaris
Experimental arm
Control arm
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prednisolone 80 mg tapered
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prednisolone 80 mg tapered
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azathioprine 3 mg/kg
2
azathioprine 3 mg/kg
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oral dexamethasone 300 mg pulses (6 x 50 mg tabs)
on three consecutive days per month
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oral placebo pulses (6 tabs) on three consecutive
days per month
primary endpoint number of weeks in complete
remission out of 52 weeks hypothesis 10 weeks
longer complete remission in treated group a
5 power 90 desired sample size 2 x 9
Mentink et al. Arch Dermatol 2006
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Typical case of remission
prednisolone (mg/day)
80
60
40
duration of remission
20
8
9
11
12
10
1
6
7
5
4
3
2
time (months)
initial control
remission
Mentink et al. Arch Dermatol 2006
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Typical case with relapse
prednisolone (mg/day)
80
60
40
duration of remission
20
8
9
11
12
10
1
6
7
5
4
3
2
time (months)
initial control
relapse
initial control
remission
Mentink et al. Arch Dermatol 2006
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Outcome
Mentink et al. Arch Dermatol 2006
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Mean dose of prednisolone
Mentink et al. Arch Dermatol 2006
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Adverse events and tolerability

• Adverse eventsDP 30 adverse events in 10/11
  patients. PP 14 adverse events in 5/9 patients.
• Discontinuation of treatmentDP 3 patients
  infection, myalgia, high blood glucose, and
  cognitive dysfunction. PP 0 patients.
• Weight gain of more than 5 from baselineDP
  8/11, mean increase 12.4PP 1/9, mean increase
  2.9 (p lt0.05).

Mentink et al. Arch Dermatol 2006
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Conclusions

• We were unable to prove whether oral
  dexamethasone pulse therapy had an additive
  beneficial effect over a conventional regimen of
  a prednisolone 80 mg tapering schedule and
  azathioprine 3 mg/kg/day, in terms of time to
  remission, duration of remission, or cumulative
  prednisolone dose.
• Dexamethasone pulse therapy induces more adverse
  events in PV, in particular a higher weight gain.
  
• Conventional treatment with prednisolone 80
  mg/day on a tapering schedule to zero over 19
  weeks and azathioprine 3 mg/kg -continued for one
  year after tapering- alone, is an effective
  therapy for PV.

Mentink et al. Arch Dermatol 2006
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Randomized placebo-controlled trials in pemphigus
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Randomized placebo-controlled trials in pemphigus
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Randomized placebo-controlled trials in pemphigus
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Rituximab (anti-CD20) in treatment of pemphigus

• open series and cases (?n111)
• Joly et al., NEJM 2008 86 free of disease
  after 3 y
• cure of chronic disease!
• pemphigus not labelled by Roche

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Murrell et al. JAAD 2008
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Murrell et al. JAAD 2008
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Pemphigus outcome measures group meeting Otsu 2008
Photo Dedee Murrell
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How do I treat pemphigus?

• mild
• class III/IV corticosteroid creme / intralesional
  injection
• severe
• prednisolon 80 mg, taper in 5 months

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Tapering of prednisolon
prednisolone (mg/day)
80
60
40
20
8
9
11
12
10
1
6
7
5
4
3
2
time (months)
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How do I treat pemphigus?

• mild
• class III/IV corticosteroid creme / intralesional
  injection
• severe
• prednisolon 80 mg, taper in 5 months

• azathioprine 3 mg/kg (1.5 mg/kg gt60 years or low
  TPMT)continue gt1 year after tapering steroid
• mycophenolate mofetil 2000 g or mycophenolic acid
  1440 mg
• rituximab 2 x 500 mg per year
• HIVIG 5 x 200g per month

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Acknowledgmentsstaff and residents dermatology
Groningen