Can Otezla (apremilast) be used to treat refractory oral ulcers in an adult with Behçet’s disease, and what is the appropriate dosing and monitoring?

Apremilast (Otezla) for Refractory Oral Ulcers in Behçet's Disease

Apremilast 30 mg twice daily is an effective and FDA-approved treatment option for refractory oral ulcers in Behçet's disease when topical corticosteroids and colchicine have failed, and it should be strongly considered before escalating to biologics or other immunosuppressants in patients without major organ involvement. 1, 2

When to Use Apremilast

Apremilast should be initiated when:

• Oral ulcers remain refractory to first-line therapy (topical corticosteroids plus colchicine) 1
• The patient has contraindications to or has failed azathioprine, interferon-α, or TNF-α inhibitors 1
• The patient requires systemic therapy but has isolated mucocutaneous disease without major organ involvement 1

The 2018 EULAR guidelines specifically endorse apremilast "in selected cases" for mucocutaneous manifestations of Behçet's disease, based on randomized controlled trial data showing significant reduction in oral ulcer number and pain 1, 3.

Dosing and Titration

Standard dosing is apremilast 30 mg twice daily. 2, 4, 3 The medication should be titrated according to the FDA-approved schedule to minimize gastrointestinal side effects, though the evidence does not specify the exact titration schedule in these studies. 2

Expected Efficacy and Timeline

Clinical improvement typically occurs within 12 weeks:

• Mean oral ulcer count decreases significantly (from 3.3 to 0.58 ulcers) 5
• Pain reduction of approximately 45 mm on a 100-mm visual analog scale 3
• Complete or partial response rates are substantial, with benefits sustained through 64 weeks of continued treatment 6
• Disease activity scores (BSAS, BDCAF) and quality of life measures show significant improvement 5

Real-world data from multiple cohorts confirm these trial results, with rapid and maintained improvement even in patients refractory to multiple conventional and biologic therapies 4, 5.

Steroid-Sparing Benefits

Apremilast enables corticosteroid tapering or discontinuation:

• Complete steroid discontinuation achieved in approximately 50% of patients 5
• Colchicine can often be discontinued as well (67% of patients in one study) 5
• This steroid-sparing effect is particularly valuable for long-term management 1

Critical Contraindications and Limitations

Do NOT use apremilast for major organ involvement in Behçet's disease:

• Ocular disease (uveitis, retinal vasculitis) requires more aggressive immunosuppression 1, 7
• Vascular involvement (cerebral venous thrombosis, deep vein thrombosis) requires corticosteroids plus immunosuppressives like azathioprine or cyclophosphamide 8, 7
• Neurological involvement (neuro-Behçet's) requires aggressive therapy, not apremilast 8, 1
• Gastrointestinal involvement requires stronger immunosuppression 1, 7

Apremilast is specifically indicated only for mucocutaneous disease—oral and genital ulcers—not for systemic manifestations. 1, 2

Adverse Effects and Monitoring

The most common adverse events are gastrointestinal:

• Diarrhea, nausea, and vomiting occur frequently (40% experienced nausea in one cohort) 3, 6
• These side effects typically occur early and may improve with continued use 2, 6
• In real-world practice, gastrointestinal adverse events led to discontinuation in approximately 33% of patients in one Italian cohort 5
• Headache and upper respiratory tract infections are also common 6

No specific laboratory monitoring is required, which is an advantage over azathioprine or other immunosuppressives. 2 However, weight loss can occur and should be monitored, particularly in patients with low baseline body weight. 2

Combination Therapy Strategy

Apremilast can be combined with topical corticosteroids during the initial treatment phase to enhance symptomatic relief while the systemic medication takes effect. 1 This approach allows for:

• Immediate pain control with topical agents (clobetasol 0.05% gel for localized lesions or dexamethasone 0.1 mg/mL mouth rinse for widespread lesions) 1, 9
• Systemic disease modification with apremilast 1
• Gradual tapering of topical and systemic steroids as apremilast achieves control 1, 5

Positioning in Treatment Algorithm

The treatment hierarchy for oral ulcers in Behçet's disease is:

1. First-line: Topical corticosteroids (clobetasol 0.05% gel or dexamethasone 0.1 mg/mL rinse) plus colchicine 8, 1, 9

2. Second-line (refractory cases): Apremilast 30 mg twice daily 1, 4

3. Third-line (apremilast failure or major organ involvement): Azathioprine, interferon-α, or TNF-α inhibitors 8, 1

This positioning reflects both guideline recommendations and the practical reality that apremilast offers an oral, well-tolerated option before committing to injectable biologics or more toxic immunosuppressives. 1, 2, 4

Common Pitfalls to Avoid

• Do not use apremilast as monotherapy for patients with active major organ disease—these patients need aggressive immunosuppression from the outset 1, 7
• Do not discontinue apremilast prematurely if gastrointestinal side effects occur; many patients tolerate these effects with continued use, though some will require discontinuation 5, 6
• Do not expect immediate results—assess efficacy at 12 weeks, not earlier 3, 6
• Do not forget to optimize oral hygiene and topical measures even when using systemic therapy 8, 9