SHEFFIELD, England -- Pentoxifylline (Trental) does not appear effective as a first-line therapy against recurrent aphthous stomatitis, but the drug may be useful as second-line therapy.
SHEFFIELD, England, May 1 -- Pentoxifylline (Trental) does not appear effective as a first-line therapy against recurrent aphthous stomatitis, but the drug may be useful as second-line therapy.
So concluded investigators here who conducted the first rigorous clinical trial of pentoxifylline for this mouth-ulcerating condition. However, the study involved only 26 patients.
Patients taking the drug had smaller and fewer ulcers, less pain, and more ulcer-free days compared with those on placebo, reported Martin H. Thornhill, MBBS, Ph.D., of the University of Sheffield School of Clinical Dentistry, and colleagues.
The differences were small, however, and only the reduction in ulcer size proved to be statistically significant (P=.05), they reported in the April issue of Archives of Dermatology.
Previous studies of the drug for this indication had been encouraging, with the authors of one study going so far as to claim pentoxifylline induced long-term remission of recurrent aphthous stomatitis. "Unfortunately, all the reported studies have been open-label without a placebo control," Dr. Thornhill said.
The current study was the first double-blind, placebo-controlled study of pentoxifylline for recurrent aphthous stomatitis. The 26 patients were randomized to 400 mg of pentoxifylline three times a day or a look-alike placebo for 60 days.
The treatment group reported a greater proportion of ulcer-free days compared with the placebo group (46% versus 38%; P=.43). The treatment group also tended to have a small reduction in median pain score from baseline compared with a small increase for the placebo group (-0.21 versus 0.38; P=.24). The treatment group also tended to have greater reduction in the median number of ulcers from baseline (-0.32 versus -0.05; P=.30).
Finally, the treatment group experienced a significant reduction in median ulcer size compared with an increase for the placebo group (-0.39 versus 0.27; P=.05).
Adverse events were not inconsiderable, however, affecting 69% of the treatment group compared with 50% of the placebo group. In both groups, the most common events included dizziness, headaches, upset stomach, nausea, and increased heart rate.
"Thus, given the potential for significant adverse effects and the small benefits of the drug demonstrated in this clinical trial, we cannot recommend pentoxifylline as the drug of first choice for treatment of recurrent aphthous stomatitis, although it may have a second-line role in the management of patients unresponsive to other treatments or as an adjunct to other treatments," Dr. Thornhill and colleagues concluded.
Recurrent aphthous stomatitis affects anywhere from 20% to 50% of the general population, and there is no satisfactory treatment, said Alison Bruce, M.D., and Roy S. Rogers III, M.D., of the Mayo Clinic in Rochester, Minn., in an accompanying editorial.
Topical corticosteroids are the mainstay of treatment at most institutions, but the treatment is palliative and does not reduce the number of attacks, Dr. Bruce and Dr. Rogers said.
"The results of the study are somewhat disappointing when compared with previous open trials that very positively and enthusiastically suggested that pentoxifylline may completely or almost completely resolve ulceration for several months after therapy, and therefore, unlike other existing treatments, lead to sustained remission," they said.
However, the results should be interpreted cautiously because of the small sample size and short treatment period, they said. The study was too small to preclude the validation of any drug benefit, and the 60-day study period may have been too short to accurately assess the drug's effect, they said.
The study "reminds us to be cautious about overly enthusiastic open studies and paves the way for further trials with more patients and longer treatment periods to effectively determine whether pentoxifylline may have a role in recurrent aphthous stomatitis management," they concluded.
Pentoxifylline is a nonselective phosphodiesterase inhibitor commonly used for treating circulation problems such as intermittent claudication. The drug also inhibits tumor necrosis factor alpha and may block other proinflammatory cytokines as well, the study authors said.