Low-dose methotrexate combined with topical betamethasone dipropionate was a safe and effective treatment for bullous pemphigoid in a retrospective study conducted by Dr. Petra Kjellman and colleagues.
For the past 50 years, glucocorticoids have been the mainstay of treatment for bullous pemphigoid (BP), but the high doses of these drugs that are typically needed to control inflammation are poorly tolerated, particularly among the elderly, who are most commonly affected, according to the researchers.
To minimize the adverse effects of glucocorticoids, which include sepsis, pneumonia, gastrointestinal tract bleeding, diabetes, and osteoporosis, other immunosuppressants also have been tried as steroid-sparing agents in BP, but few controlled trials have been done, they noted.
For the past decade, Dr. Kjellman and colleagues from the department of dermatology and venereology, Karolinska University Hospital, Stockholm, have preferentially used methotrexate for BP patients, with prednisone if needed or if methotrexate could not be given or tolerated.
The usual regimen involved an initial dosage of 5 mg/week of methotrexate, with topical betamethasone dipropionate applied twice daily until the disease was controlled. If necessary, methotrexate dosage was increased by 2.5 mg/week.
If symptoms persisted despite methotrexate treatment, prednisone was added in doses of 10-20 mg/day, and if methotrexate could not be given because of anemia, liver disease, or renal failure, prednisone was given alone.
Between 1999 and 2003, 138 patients whose mean age was 81 years were diagnosed with BP. Of these, 57% were women, 51% had mild disease, 38% had moderate disease, and 11% had severe disease.
Methotrexate treatment was initiated in 98 (71%), with a median weekly dosage of 5 mg. Among these patients, 61 continued on methotrexate monotherapy (group 1) and had a mean cumulative dose of 280 mg.
Among patients who received methotrexate, 37 also were treated with prednisone (group 2). The median weekly dosage of methotrexate in this group was 6 mg, and the median cumulative dose was 440 mg.
Forty patients did not receive methotrexate, with 15 receiving high-dose prednisone alone at a median daily dosage of 12 mg and with a median cumulative dose of 4,000 mg (group 3). The other 25 patients who did not receive methotrexate (group 4) had mild disease and were managed with topical betamethasone gel alone.
Median follow-up was 26 months. At 24 months, the remission rates were 43% in group 1, 35% in group 2, 0% in group 3, and 83% in group 4 (Arch. Dermatol. 2008;144:612-16).
Mortality in BP is considerable, with previous reports finding 1-year mortality ranging from 10% to 41%, according to the researchers. In this series, 2-year survival was 65%, 67%, 47%, and 52% in the four groups, respectively, and there was a tendency toward better survival for the methotrexate-treated patients, with median survival times of 38 and 24 months in groups 1 and 2, respectively.
Only one patient in this series developed anemia, and although elevated liver enzymes were seen on occasion during the first weeks of therapy, normalization usually followed within 4-6 weeks. They did not perform pretreatment liver biopsies.
They researchers noted that they are also developing a BP quality register and biobank to enable further follow-up of these patients, and they plan a prospective study to provide further information. They had no conflicts of interest to disclose.