Table 8.
Controlled trials reporting effectiveness of systemic treatments for recurrent aphthous stomatitis (RAS).*
| Author, Year | Therapy and Regimen | Treatment Arms (n)† |
Mean age‡ |
Trial Duration |
Outcome/Adverse Events (AE) | OCEBM Quality rating - Sources of bias |
|---|---|---|---|---|---|---|
| Thornhill et al., 2007 | Pentoxifylline (400 mg TID; PX) vs. Placebo TID | PX (14-3) PL (12-4) | 33–34 | 2 months (plus 2 pre/post) | Reduced ulcer size with PX (p=0.05) but minimal benefits seen for other parameters. AE in both arms. | 2B – 27% total attrition, small sample size, only self-reported outcomes (diaries). |
| Preshaw et al., 2007 | Doxycycline (20 mg BID; DX) vs. placebo BID | DX (25)§ PL (25)§ | 37–43 | 3-month | More days with no new RAS with DX (p=0.04). Other parameters tended to improve, though not significantly. AE unknown. | 2B – Attrition and compliance unknown, only self-reported outcomes (diaries). |
| Samet et al., 2007 | Bee propolis (500 mg QD; BP) vs. Placebo (calcium-based supplement QD; PL) | BP (10-0) PL (9-2) | Not stated (≥18) | 6–13 months | Higher % of patients on BP with ≥50% reduction in # of outbreaks (p=0.06) and improved quality of life (QoL; p=0.03). AE unknown. | 2B – Only self-reports, PL may not be inert, small sample, incomplete baseline results, 10.5% attrition, randomization method unknown, QoL data collection not standardized. |
| Yazdanpanah et al., 2008 | Poliovirus vaccine (4 drops at baseline; PV) vs. Placebo (PL) | PV (20)§ PL (28)§ | 29–30 | 3 months | Fewer symptoms with PV (p<0.01). No AE. | 2B – PL and blinding not described, attrition unknown, only self-reported outcomes, some PV contained antibiotics. |
| Sharquie et al., 2008 | Zinc sulfate (150 mg BID; ZN) vs. Dapsone (50 mg BID; DP) vs. Placebo (glucose, 250 mg BID) | ZN (15)§ DP (15)§ PL (15)§ | 31 | 3 months | Significantly smaller size and fewer manifestations with ZN or DP vs. PL at weeks 4–12. No AE. | 2B – PL may not be inert, no randomization reported, small sample, multiple comparisons, attrition unknown. |
| Davatchi et al., 2009‖ | Colchicine (1 mg QD; CO) vs. Placebo (PL) | CO/PL (169) | 32 | 4 months, then cross over | Fewer ulcers with CO (p<0.005). AE in both groups, with increased liver enzymes in 2 patients on CO. | 2B – Unclear design (sample size, attrition, PL description, randomization method) and statistics. |
| de Abreu et al., 2009 | Clofazimine (100 mg QD for 30 days, then QOD; CL) vs. Colchicine (0.5 mg QID) vs. Placebo BID | CL (23)§ CO (23)§ PL (20)§ | 34–45 | 6 months | Improved number and duration, but not size, with CL vs. CO/PL (p<0.05). CO not better than PL. Gastrointestinal (CO) and cutaneous (CL) AE. | 2B – Incomplete blinding, PL regimen different from CO/CL, attrition unknown, PL older. |
| Mousavi et al., 2009 | Homeopathic (multiple treatments; HM) vs. Placebo (PL) | HM (50-0) PL (50-0) | 38 | 6 days | Less pain and smaller size at day 4 and 6 with HM (p<0.05). No dropouts due to AE. | 2B – Single (patient) blind, PL may have tasted differently, individual treatment effectiveness unknown, short trial. |
| Femiano et al., 2010 | Prednisone (0–25 mg; PN) vs. Montelukast (0- 10 mg, MK) vs. Cellulose placebo (0–100 mg, PL) QD | PN (20-0) MK (20-0) PL (20-0) | 27 | 2 months plus 2 months follow-up | Fewer RAS with PN/MK vs. PL at 1–4 months (p<0.01). Less time to healing and pain free with PN vs. MK and PN/MK vs. PL (p<0.0001). Two mild AE in each MK/PL arm, 6 AE with PN. | 2B – PN regimen different than MK/PL, initial sample size unclear, full blinding unclear, unknown if PL pill different from MK/PN, more females in PL arm, inconsistencies in results. |
| Pourahmad et al., 2010 | Camel thorn distillate (CT) vs. distilled water (PL), rinse+swallow QID | CT (49)§ PL (44)§ | 27–32 | 14 days | Less time to pain resolution in CT arm. Less size and pain with CT at days 3–7 (p<0.001) and 10 (p<0.02). AE unknown | 2B – Randomization method, dosage and attrition unknown, PL arm had larger RAS at baseline, PL may have tasted/looked differently |
*
All clinical trials were single center and they were based on a randomized, double-blind, placebo-controlled, parallel arm design including intent to treat (ITT) analysis of at least one objective outcome (i.e. confirmed by examination) unless otherwise specified. Trials that did not report presence or absence of attrition also did not mention ITT analysis.
†
Numbers in parenthesis indicate initial sample size minus number lost to follow-up, if known.
‡
In years. All trials included both genders and were conducted in idiopathic RAS patients unless otherwise specified.
§
Assumed to be the final sample size after attrition (attrition was either not reported or was not reported by each arm).
‖
BD patients.