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Dr. Alison Bruce
“Canker sores [aphthous ulcers] are very common, yet are often not well managed as the diagnosis is not always correctly made,” lead study author Alison J. Bruce, MB, ChB, said in an interview following the virtual annual meeting of the American Academy of Dermatology. “They’re often mistaken for herpes infection and therefore treated with antiviral therapy. Of the available therapies, several have common side effects or require lab monitoring or are not uniformly effective.”
In their poster abstract, Dr. Bruce, of the division of dermatology at the Mayo Clinic, Jacksonville, Fla., and colleagues noted that, while no principal etiology has been established for recurrent aphthous stomatitis (RAS), immune up-regulation plays a role in the pathogenesis of the condition. “Attacks of RAS may be precipitated by local trauma, stress, food intake, drugs, hormonal changes and vitamin and trace element deficiencies,” they wrote. “Local and systemic conditions and genetic, immunological and microbial factors all may play a role in the pathogenesis.”
Apremilast, a phosphodiesterase-4 inhibitor, down-regulates inflammatory response by modulating expression of tumor necrosis factor–alpha; interferon-gamma; and interleukin-2, IL-12, IL-17, and IL-23. It is approved by the Food and Drug Administration for treating plaque psoriasis and psoriatic arthritis, and in July 2019, was approved for treating ulcers associated with Behçet’s disease, in adults.*
For the pilot study, the researchers enrolled 15 patients with RAS to receive apremilast 30 mg twice daily for 15 weeks after 1 week titration. To be eligible for the trial, patients must have had monthly oral ulcers in preceding 6 months, at least two ulcers in previous 4 weeks prior to enrollment at baseline, at least three ulcers during flares, inadequate control with topical therapy, and no evidence of systemic disease. They excluded patients on immune-modulating therapy or systemic steroids, pregnant or breastfeeding women, those with a systemic infection, those with a history of recurrent bacterial, viral, fungal, or mycobacterial infection, those with a history of depression, as well as those with a known malignancy or vitamin deficiencies. Patients were assessed monthly, evaluating number of ulcers, visual analog pain scale, physician’s global assessment and Chronic Oral Mucosal Disease Questionnaire (COMDQ).
Dr. Bruce and colleagues found that, within 4 weeks of therapy, complete clearance of RAS lesions occurred in all patients except one in whom ulcers were reported to be less severe. That patient had considerable reduction in number, size, and duration of oral ulcers. Remission in all patients was sustained during 16 weeks of treatment. COMDQ responses improved considerably from baseline to week 8, and this was continued until week 16.
“Onset of response [to apremilast] was rapid,” Dr. Bruce said. “For many other therapies, patients are counseled that [they] may take several weeks to become effective. Response was also dramatic. Almost all patients had complete remission from their ulcers, compared with other therapies where oftentimes reduction or attenuation is achieved, as opposed to complete resolution. There was a suggestion that a lower dose [of apremilast] may still be effective. This adds to our ‘toolbox’ of therapeutic options.”
The most common adverse effects were nausea/vomiting and headache, but these were mild and tolerable and generally resolved by week 4.
The researchers acknowledged certain limitations of the study, including its small sample size. “The challenge will most likely be insurance coverage,” Dr. Bruce said. “This is unfortunate, as it would be ideal to offer a safe treatment without the need for monitoring.”
The investigator-initiated study was supported by Celgene. The researchers reported having no financial disclosures.
SOURCE: Bruce AJ et al. AAD 20, Abstract 17701.
*Correction 6/23/2020: An earlier version of this story misstated the approved indications for apremilast.