Cochrane · intervention · CD011018
Interventions for managing oral ulcers in Behçet's disease
Taylor, J, Glenny, AM, Walsh, T, et al. · Cochrane Database of Systematic Reviews · 2014 · Cochrane Library
Full textEvery question was extracted from the full review (methods and results), not only its Summary of Findings table.
Questions
33
current version
GRADE rated
1
No studies
0
Included studies
15
as reported
No studies 0 · 0%Ungraded 32 · 97%Very low 0 · 0%Low 0 · 0%Moderate 1 · 3%High 0 · 0%
Ungraded means an effect was reported without a GRADE rating; it is not a gap. No studies means the review found nothing to answer the question. The six categories are a display order, not a score.
Review question
| Element | Planned (methods) | Found (results) |
|---|---|---|
| Population | Participants with Behcet's disease with a history of recurrent oral aphthous-type (RAS-type) ulcers diagnosed clinically (additional systemic diseases noted where reported) | People with Behcet's disease (RAS-type oral ulceration); 15 RCTs, n=888 randomised (780 evaluated); 11 trials Turkey, 2 Japan, 1 Iran, 1 UK; most used the ISG 1990 criteria |
| Intervention | Any preventive, palliative, or curative intervention administered systemically or topically | Sucralfate (n=2); Interferon-alpha topical (n=2); Cyclosporin A topical (n=1); Triamcinolone acetonide ointment (n=1); Aciclovir (n=1); Thalidomide (n=1); Depot corticosteroids (n=1); Rebamipide (n=1); Etanercept (n=1); Colchicine (n=2); Interferon-alpha systemic (n=1); Cyclosporin systemic (n=1) |
| Comparison | Standard care; no active treatment; placebo; or another active intervention (head-to-head) | Placebo (n=13); Phenytoin syrup mouthwash (n=1); Interferon-alpha 2000 IU (n=1); Colchicine (n=1) |
| Outcomes | Primary: pain associated with oral ulcers; episode duration; episode frequency; safety of the intervention including adverse effects. Secondary: patient-reported change in quality of life or morbidity | Pain associated with oral ulcers (n=6); Episode frequency / number of oral ulcers (n=13); Episode duration / healing time (n=4); Safety of the intervention including adverse effects (n=12); Quality of life (n=1, tool used but no data reported) |
| Study designs | RCTs (including cross-over trials with adequate washout, and split-mouth studies with no risk of contamination); trials of interventions for systemic manifestations of Behcet's disease reporting pre-specified oral ulcer outcomes | RCT (n=15; 1 low risk of bias, 1 unclear, 13 high risk of bias); 14 parallel, 1 cross-over |
| Timing | Not specified | End of treatment and end of follow-up (timing of outcome measurement varied widely across trials) |
Search date: 2013-10. Databases: Cochrane Oral Health Group Trials Register; Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 9); MEDLINE via Ovid (1946 to 2013); EMBASE via Ovid (1980 to 2013); CINAHL via EBSCO (1980 to 2013); AMED via Ovid (1985 to 2013); ClinicalTrials.gov; WHO ICTRP
Questions and results
Current version onlyTopical interventions (sucralfate, interferon-alpha, cyclosporin A) vs Placebo
Population: People with Behcet's disease with a history of recurrent oral aphthous-type (RAS-type) ulcers diagnosed clinically; primary care
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Episode frequency associated with oral ulcers | SoF (topical interventions vs placebo), grouped comment spanning all four listed outcomes (verbatim): "5 placebo-controlled trials evaluated topical interventions (sucralfate suspension (2 trials), interferon-alpha (2… | NR | Ungraded |
Safety of the intervention including adverse effects | SoF (topical interventions vs placebo), grouped comment spanning all four listed outcomes (verbatim): "5 placebo-controlled trials evaluated topical interventions (sucralfate suspension (2 trials), interferon-alpha (2… | NR | Ungraded |
Pain associated with oral ulcers | SoF (topical interventions vs placebo), grouped comment spanning all four listed outcomes (verbatim): "5 placebo-controlled trials evaluated topical interventions (sucralfate suspension (2 trials), interferon-alpha (2… | NR | Ungraded |
Episode duration associated with oral ulcers | SoF (topical interventions vs placebo), grouped comment spanning all four listed outcomes (verbatim): "5 placebo-controlled trials evaluated topical interventions (sucralfate suspension (2 trials), interferon-alpha (2… | NR | Ungraded |
Systemic interventions (aciclovir, thalidomide, corticosteroids, rebamipide, etanercept, colchicine, interferon-alpha) vs Placebo
Population: People with Behcet's disease with a history of recurrent oral aphthous-type (RAS-type) ulcers diagnosed clinically; primary care
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Pain associated with oral ulcers | SoF 2 (systemic interventions vs placebo), grouped comment spanning all four listed outcomes (verbatim; the review's wording "topical" is a typo for systemic): "8 placebo-controlled trials evaluated topical… | NR | Ungraded |
Episode duration associated with oral ulcers | SoF 2 (systemic interventions vs placebo), grouped comment spanning all four listed outcomes (verbatim; the review's wording "topical" is a typo for systemic): "8 placebo-controlled trials evaluated topical… | NR | Ungraded |
Safety of the intervention including adverse effects | SoF 2 (systemic interventions vs placebo), grouped comment spanning all four listed outcomes (verbatim; the review's wording "topical" is a typo for systemic): "8 placebo-controlled trials evaluated topical… | NR | Ungraded |
Episode frequency associated with oral ulcers | SoF 2 (systemic interventions vs placebo), grouped comment spanning all four listed outcomes (verbatim; the review's wording "topical" is a typo for systemic): "8 placebo-controlled trials evaluated topical… | NR | Ungraded |
Sucralfate suspension (topical) vs Placebo suspension
Population: People with Behcet's disease with a history of recurrent oral aphthous-type (RAS-type) ulcers diagnosed clinically; primary care
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Mean duration of episodes End of treatment | MD -1.00 [-5.69, 3.69] | 1 study · 35 participants | Ungraded |
Healing time End of treatment (3 months) | MD -1.09 [-2.61, 0.43] | 1 study · 30 participants | Ungraded |
Number of painful days End of treatment | MD 9.00 [-4.25, 22.25] | 1 study · 35 participants | Ungraded |
Number of episodes End of treatment | MD 1.40 [-0.15, 2.95] | 1 study · 35 participants | Ungraded |
Pain (0-3 scale) End of treatment (3 months) | MD -0.38 [-0.87, 0.11] | 1 study · 30 participants | Ungraded |
Frequency of oral ulcers End of treatment (3 months) | MD -0.80 [-2.12, 0.52] | 1 study · 30 participants | Ungraded |
Interferon-alpha (topical; hydrogel or lozenges) vs Placebo
Population: People with Behcet's disease with a history of recurrent oral aphthous-type (RAS-type) ulcers diagnosed clinically; primary care
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Total number of oral ulcers 24 weeks (duration of treatment) | MD 1.50 [-10.43, 13.43] | 1 study · 61 participants | Ungraded |
Total ulcer burden | Kilic 2009 (interferon-alpha lozenges 1000 IU or 2000 IU vs placebo, 84 patients; high risk of selective reporting): the data presented did not allow analysis; authors reported no statistically significant difference… | 1 study · 84 participants | Ungraded |
Quality of life | Kilic 2009 described the use of a quality of life assessment tool but did not report any quality of life data. | 1 study · 84 participants | Ungraded |
Cyclosporin A in orabase (topical) vs Placebo (orabase)
Population: People with Behcet's disease with a history of recurrent oral aphthous-type (RAS-type) ulcers diagnosed clinically; primary care
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Safety of the intervention including adverse effects | Ergun 1997: no adverse effects were seen. | 1 study · 24 participants | Ungraded |
Oral ulcers (number, size, healing time) | Ergun 1997 (cyclosporin A in orabase vs placebo orabase, 24 patients; high risk of reporting bias): no data were presented; authors reported no clinical improvement in the number, size, and healing time of ulcers for… | 1 study · 24 participants | Ungraded |
Triamcinolone acetonide 0.1% ointment (topical) vs Phenytoin syrup mouthwash (30 mg in 5 mL)
Population: People with Behcet's disease with a history of recurrent oral aphthous-type (RAS-type) ulcers diagnosed clinically; primary care
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Positive response (not defined) 7 days | RR 1.63 [1.13, 2.34] | 1 study · 60 participants | Ungraded |
Interferon-alpha 1000 IU lozenges (topical) vs Interferon-alpha 2000 IU lozenges (topical)
Population: People with Behcet's disease with a history of recurrent oral aphthous-type (RAS-type) ulcers diagnosed clinically; primary care
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Total ulcer burden Interferon-alpha dose comparison | Kilic 2009 (interferon-alpha 1000 IU vs 2000 IU lozenges, 84 patients): the data presented did not allow analysis; authors reported no statistically significant difference in total ulcer burden between the two doses. | 1 study · 84 participants | Ungraded |
Aciclovir (systemic; 800 mg 5x/day for 1 week then 400 mg 2x/day for 11 weeks) vs Placebo
Population: People with Behcet's disease with a history of recurrent oral aphthous-type (RAS-type) ulcers diagnosed clinically; primary care
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Frequency of oral ulcers | Davies 1988 (aciclovir vs placebo, 36 patients, cross-over; high risk of reporting bias; concomitant treatments): data were not presented in a usable format; authors reported no statistically significant difference in… | 1 study · 36 participants | Ungraded |
Thalidomide (systemic; 100 mg or 300 mg daily) vs Placebo
Population: People with Behcet's disease with a history of recurrent oral aphthous-type (RAS-type) ulcers diagnosed clinically; primary care
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Safety of the intervention including adverse effects Males only | Hamuryudan 1998: significant adverse effects including severe sedation, polyneuropathy, loss of libido, and weight gain; a greater number of adverse events was seen for the higher (300 mg) dose; 4 patients withdrew due… | 1 study · 101 participants | Ungraded |
Number of (minor aphthous) oral ulcers Males only | Hamuryudan 1998 (thalidomide 100 mg or 300 mg daily vs placebo, 101 male patients; high risk of reporting bias): a significant effect on mean numbers of minor oral ulcers was reported from week 4 in both thalidomide… | 1 study · 101 participants | Ungraded |
Depot corticosteroids (systemic; 40 mg methylprednisolone IM every 3 weeks for 27 weeks) vs Placebo (saline IM injection)
Population: People with Behcet's disease with a history of recurrent oral aphthous-type (RAS-type) ulcers diagnosed clinically; primary care
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Mean number of oral ulcers End of treatment (week 27) | MD 0.00 [-0.47, 0.47] | 1 study · 85 participants | Ungraded |
Rebamipide (systemic; 300 mg daily) vs Placebo
Population: People with Behcet's disease with a history of recurrent oral aphthous-type (RAS-type) ulcers diagnosed clinically; primary care
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Global aphthae count and pain score | Matsuda 2003 (rebamipide 300 mg daily vs placebo, 35 patients; high risk of reporting bias; concomitant treatments): authors stated that rebamipide improved the global evaluation aphthae count and global evaluation… | 1 study · 35 participants | Ungraded |
Etanercept (systemic; 25 mg subcutaneously twice weekly for 4 weeks) vs Placebo (subcutaneous)
Population: People with Behcet's disease with a history of recurrent oral aphthous-type (RAS-type) ulcers diagnosed clinically; primary care
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Mean number of oral ulcers Males only | Melikoglu 2005 (etanercept 25 mg s.c. twice weekly for 4 weeks vs placebo, 40 male patients; high risk of reporting bias): authors reported a statistically significant difference in mean number of oral ulcers with… | 1 study · 40 participants | Ungraded |
Colchicine (systemic; 0.5 mg weight-adjusted daily) vs Placebo
Population: People with Behcet's disease with a history of recurrent oral aphthous-type (RAS-type) ulcers diagnosed clinically; primary care
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Total number of oral ulcers 24 months | MD 2.30 [-3.42, 8.02] | 1 study · 115 participants | Moderate Downgraded: imprecision |
Improvement in oral ulcer score 6 months | RR 0.75 [0.48, 1.17] | 1 study · 28 participants | Ungraded |
Interferon-alpha (systemic; 6 x 10^6 IU subcutaneously 3x/week for 3 months) vs Placebo (subcutaneous)
Population: People with Behcet's disease with a history of recurrent oral aphthous-type (RAS-type) ulcers diagnosed clinically; primary care
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Duration and pain of oral ulceration | Alpsoy 2002 (subcutaneous interferon-alpha 6 x 10^6 IU 3x/week for 3 months vs placebo, 50 patients; high risk of reporting bias): data were not presented in a usable format; authors reported a statistically… | 1 study · 50 participants | Ungraded |
Safety of the intervention including adverse effects | Alpsoy 2002: high rate of adverse events including alopecia, leukopenia, and diarrhoea; 18 of 23 patients in the treatment arm experienced mild flu-like symptoms. | 1 study · 50 participants | Ungraded |
Cyclosporin (systemic; 10 mg/kg/day) vs Colchicine (systemic; 1 mg daily)
Population: People with Behcet's disease with a history of recurrent oral aphthous-type (RAS-type) ulcers diagnosed clinically; primary care
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Safety of the intervention including adverse effects | Masuda 1989: multiple adverse events in the cyclosporin arm; 3 patients withdrew and 9 had a dose reduction as a result. | 1 study · 92 participants | Ungraded |
Alleviation of oral aphthous ulcers 16 weeks | RR 3.3 [1.85, 5.88] | 1 study · 92 participants | Ungraded |
Any active intervention for oral ulcers (preventive, palliative, or curative), administered systemically or topically vs No active treatment, placebo, or another active intervention (head-to-head)
Population: People with Behcet's disease with a history of recurrent oral aphthous-type (RAS-type) ulcers diagnosed clinically; primary care
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Safety of the intervention including adverse effects | no estimate extracted | NR | No studies |
Episode frequency associated with oral ulcers | no estimate extracted | NR | No studies |
Episode duration associated with oral ulcers | no estimate extracted | NR | No studies |
Pain associated with oral ulcers | no estimate extracted | NR | No studies |
Quality of life or patient-reported change in morbidity | no estimate extracted | NR | No studies |