Apremilast (Otezla) for Oral Ulcers in Behçet's Disease
Apremilast 30 mg twice daily is an appropriate and FDA-approved treatment for oral ulcers in Behçet's disease, particularly for patients who have failed conventional therapies like topical steroids and colchicine. 1, 2
Treatment Algorithm for Oral Ulcers in Behçet's Disease
First-Line Therapy
- Start with topical corticosteroids (clobetasol 0.05% gel for localized ulcers or dexamethasone 0.1 mg/ml mouth rinse for widespread ulcers) combined with colchicine for prevention of recurrent mucocutaneous lesions, especially when genital ulcers or erythema nodosum are present. 3
Second-Line Therapy: When to Use Apremilast
- Consider apremilast when oral ulcers are refractory to topical steroids and colchicine, or when patients require systemic therapy but have contraindications to or have failed azathioprine, interferon-alpha, or TNF-alpha inhibitors. 3
- Apremilast is specifically mentioned in the 2018 EULAR guidelines as an option "in selected cases" for mucocutaneous involvement. 3
Apremilast Dosing Regimen
Standard Dosing
- Apremilast 30 mg orally twice daily (no titration mentioned in the pivotal trials, though package inserts typically recommend titration). 1, 4, 2
- Treatment duration: Expect clinical response within 12 weeks, with sustained benefits documented up to 64 weeks. 1, 2
Expected Efficacy
- In the phase 3 trial, apremilast reduced the area under the curve for oral ulcers by 92.6 compared to placebo (P<0.001). 2
- Mean number of oral ulcers at 12 weeks: 0.5 ulcers with apremilast vs. 2.1 with placebo. 4
- Pain reduction: 44.7 mm decrease on visual analog scale vs. 16.0 mm with placebo. 4
- Real-world data from 51 patients with refractory disease showed improvement even in patients who had failed multiple biologics. 5
Monitoring and Safety Considerations
Common Adverse Events to Counsel Patients About
- Gastrointestinal symptoms are the most common: diarrhea (22% of patients), nausea (16%), and vomiting (16%) in clinical trials. 4, 2
- Headache is also frequently reported. 2
- These adverse events typically occur early in treatment and may improve with continued use. 1
Monitoring Parameters
- No specific laboratory monitoring is required for apremilast, unlike azathioprine or other immunosuppressives. 1
- Monitor clinical response by tracking number of oral ulcers, pain scores, and quality of life measures at 12-week intervals. 2
- Assess for weight loss, as this has been reported with phosphodiesterase-4 inhibitors. 1
Critical Clinical Pearls
When Apremilast is Particularly Useful
- Patients who cannot tolerate or have contraindications to azathioprine, thalidomide, or biologics. 3, 5
- Patients with isolated mucocutaneous disease without major organ involvement (the phase 3 trial specifically excluded patients with major organ involvement). 2
- Real-world evidence suggests benefit even in refractory cases that failed biologics, including improvement in some non-aphthous manifestations like folliculitis and intestinal symptoms. 5
Important Caveats
- Apremilast is not appropriate for major organ involvement (ocular, vascular, neurological, or gastrointestinal disease), which requires more aggressive immunosuppression with azathioprine, cyclophosphamide, or biologics. 3, 2
- The drug was studied specifically in patients without prior biologic exposure in the phase 3 trial, though real-world data shows efficacy in biologic-experienced patients. 5, 2
- Gastrointestinal side effects may limit tolerability in approximately 20-40% of patients, though most are mild-to-moderate. 4, 2