Behçet’s disease is a chronic inflammatory vasculitis that can affect multiple systems and most commonly appears in the third decade. Oral ulceration, ocular and genital lesions are common. Oral ulceration in Behçet’s disease resembles recurrent aphthous stomatitis (RAS) and the vast majority of Behçet’s have oral ulceration.
The aim of this review was to determine the clinical effectiveness and safety of interventions on the pain, episode duration, and episode frequency of oral ulcers and on quality of life for patients with RAS-type ulceration associated with Behçet’s disease.
Searches were conducted in The Cochrane Oral Health Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) ,Medline, Embase CINAHL and AMED databases. The US National Institutes of Health trials register and the World Health Organization (WHO) Clinical Trials Registry Platform were searched for ongoing trials. No restrictions were placed on language or date of publication.
Randomised controlled trials (RCTs) including cross-over designs with suitable washout period investigating the effects of interventions for the management of RAS-type ulceration in Behçet’s disease were included. Split mouth studies were also considered if there was no risk of contamination. Two reviewers independently selected studies and extracted data with all the review authors assessing risk of bias using the Cochrane risk of bias tool. Standard Cochrane data analysis approaches were adopted.
- 15 studies (888 patients randomised) were included. 14 used a parallel design and 1 a cross-over design.
- Only 1 study was assessed as at low risk of bias.
- 13 different interventions were assessed so it was not possible to conduct a meta-analysis.
- Topical interventions: sucralfate, interferon-alpha (different doses), cyclosporin A, triamcinolone acetonide ointment, phenytoin syrup mouthwash.
- Systemic interventions: aciclovir, thalidomide (different doses), corticosteroids, rebamipide, etanercept, colchicine, interferon-alpha, cyclosporin.
- The quality of the evidence ranged from moderate to very low and there was insufficient evidence to support or refute the use of any included intervention with regard to pain, episode duration, or episode frequency associated with oral ulcers, or safety of the interventions.
The authors concluded
Due to the heterogeneity of trials including trial design, choice of intervention, choice and timing of outcome measures, it was not possible to carry out a meta-analysis. Several interventions show promise and future trials should be planned and reported according to the CONSORT guidelines. Whilst the primary aim of many trials for Behçet’s disease is not necessarily reduction of oral ulceration, reporting of oral ulcers in these studies should be standardised and pre-specified in the methodology. The use of a core outcome set for oral ulcer trials would be beneficial.
A previous Cochrane review (Saenz et al 1998) considered pharmacological interventions for treating the different clinical features of Behçet’s disease not just oral ulceration. They included 5 studies on oral ulceration 4 of which are include in the current review. The review authors highlight the poor methodology of many of the trials and the heterogeneity of the studies. They rightly call for higher quality studies and highlight that appropriate pre-specified oral outcome measures should be used for all trials of interventions for Behçet’s disease. They also note that the development of a set of standardised outcome measures for oral ulcer trials is registered with COMET. The development of a common outcome set (COS) would be an important development as it should help reduce heterogeneity in future reviews.
Taylor J, Glenny AM, Walsh T, Brocklehurst P, Riley P, Gorodkin R, Pemberton MN. Interventions for the management of oral ulcers in Behçet’s disease. Cochrane Database of Systematic Reviews 2014, Issue 9. Art. No.: CD011018. DOI: 10.1002/14651858.CD011018.pub2
Saenz A, Ausejo M, Shea B, Wells GA, Welch V, Tugwell P. Pharmacotherapy for Behcet’s syndrome. Cochrane Database of Systematic Reviews 1998, Issue 2. Art. No.: CD001084. DOI: 10.1002/14651858.CD001084.