Apremilast for Behcet's Syndrome - A Phase 2, Placebo-Controlled Study
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Hatemi G, et al. "Apremilast for Behçet's syndrome--a phase 2, placebo-controlled study". The New England Journal of Medicine. 2015. 372(16):1510-1518.
PubMed • Full text • PDF
PubMed • Full text • PDF
Clinical Question
In patients with Behcet's Syndrome, is apremilast (a phosphodiesterase-4 inhibitor with immunomodulatory properties) safe and effective in decreasing the number of, and pain from, oral and genital ulcers?
Bottom Line
Major Points
Guidelines
Design
- Phase 2, Double-blind, multicenter, placebo-controlled, parallel-group study
- Randomly assigned @ 1:1 ratio (stratified by sex in blocks of 4) to:
- N = 111 (recruitment stopped early due to slow accrual; initial N planned as 156 for 90% power)
- 55 assigned to apremilast
- 56 assigned to placebo
- Setting: 6 University Hospitals (3 in Turkey, 3 in US)
- Enrollment: 10/2009-10/2011
- Mean follow-up:
- Analysis: Intention-to-treat; Last-observation-carried-forward used for any patients discontinuing early
Population
Inclusion Criteria
- Meet international study group definition for Behcet's Disease
- At least 18 years old
- At least 1 oral or genital ulcer within 28 days before screening
- At least 2 oral ulcers at time of randomization
Exclusion Criteria
- Patients with active involvement of a major organ during 12 months prior to enrollment
- Pregnant or breastfeeding females
- Patients with active infection
- Patients with history of recurrent or chronic infections
- Patients with latent TB
Baseline Characteristics
Interventions
- Apremilast 30 mg BID or placebo BID for 12 weeks
- After 12 weeks, all participants changed to apremilast for 12 weeks
- All then enter 4 week followup phase
- Randomized to Apremilast: |-------Apremilast x 12 weeks-------||-----Apremilast x 12 weeks-----||---4 week followup phase---|
- Randomized to Placebo: |-------Placebo x 12 weeks----------||-----Apremilast x 12 weeks-----||---4 week followup phase---|
- Apremilast dosed as 10 mg BID x2 days --> 20 mg BID x3 days --> 30 mg BID for remainder; placebo matched to this dose. Single dose reduction was allowed.
Outcomes
Comparisons are placebo group vs apremilast group
Primary Outcomes
- Number of oral ulcers at week 12
Secondary Outcomes
- Change in disease activity from baseline to week 12 based on Behcet's Disease Current Activity Form and Behcet's Syndrome Activity Score
- Change in pain from oral and genital ulcers from baseline to week 12 (visual analogue scale)
- Number of genital ulcers at week 12
- Proportion of patietns with a complete response (no oral ulcers) with respect to oral ulcers
- Proportion of patients with partial (>50% reduction in # of oral ulcers) with respect to oral ulcers
- Number of oral ulcers, pain levels from oral ulcers, Number of genital ulcers, pain from genital ulcers, disease activity at week 24
- Safety endpoints - type/frequency/severity of adverse events
Subgroup Analysis
Adverse Events
Criticisms
Funding
- Celgene (study drug manufacturer) - involved in processing, management, stat analysis, and data interpretation