Inconclusive evidence on systemic treatments for recurrent aphthous stomatitis

The trial registers of the Cochrane Oral Health and Pain, Palliative and Supportive Care Groups were searched together with The Cochrane Central database, Medline, Embase, CINHAL and AMED databases. Reference lists of relevant articles were also searched and authors of trials contacted.

Randomised controlled trials (RCTs), including those with cross-over design where the primary outcome was a reduction of pain associated with RAS, a reduction in episode duration or episode frequency were included.

Data were extracted independently by two authors and risk of bias assessment was conducted on six domains. Cochrane statistical guidelines were to be followed.

Twenty-five trials were included; 22 were placebo controlled and eight made head-to-head comparisons (five trials had more than two treatment arms). Twenty-one different interventions were assessed. The interventions were grouped into two categories: immunomodulatory/anti-inflammatory and uncertain. Only one study was assessed as being at low risk of bias. There was insufficient evidence to support or refute the use of any intervention.

No single treatment was found to be effective and therefore the results remain inconclusive in regard to the best systemic intervention for RAS. This is likely to reflect the poor methodological rigour of trials, and lack of studies for certain drugs, rather than the true effect of the intervention. It is also recognised that in clinical practice, individual drugs appear to work for individual patients and so the interventions are likely to be complex in nature. In addition, it is acknowledged that systemic interventions are often reserved for those patients who have been unresponsive to topical treatments, and therefore may represent a select group of patients.