Daniel J. Tanner

Interferon therapy for condylomata acuminata.

Current therapy for condylomata acuminata (genital warts) is not consistently effective. Therefore, we conducted a randomized, double-blind trial to compare interferon alpha-2b with placebo in the treatment of this disorder. Our rationale was that interferon has both antiproliferative and antiviral properties. The placebo or interferon (1 X 10(6) IU) was injected directly into one to three warts three times weekly for three weeks. The injections were well tolerated by both groups of patients. The side effects of fever, chills, myalgia, headache, fatigue, and leukopenia occurred more commonly in the interferon group than in the placebo group, but such effects rarely disrupted daily routines. Only 13 of 296 patients (4 percent) discontinued therapy because of side effects (11 in the interferon group and 2 in the placebo group). Twenty-six other patients were excluded from analysis because of a loss to follow-up or other deviations from protocol, thus leaving 257 patients in the final evaluation. At one week after the completion of therapy, interferon had produced a large and significantly greater reduction in mean wart area (a 62.4 percent decrease), as compared with placebo (a 1.2 percent increase in mean area) (P less than 0.001). At the conclusion of the study (13 weeks after the completion of therapy), the mean wart area was still decreased 39.9 percent below the initial size in the interferon group, whereas it had increased by 46 percent over base-line measurements in the placebo group (P less than 0.001). At the same time, all treated warts had completely cleared in 36 percent of the interferon recipients and in 17 percent of the placebo recipients (P less than 0.001), whereas treated warts progressed in 13 percent of the interferon recipients and in 50 percent of the placebo recipients (P less than 0.001). We conclude that injection of interferon alpha-2b directly into genital warts appears to be an effective and fairly well-tolerated form of therapy.

Treatment of basal cell carcinoma with intralesional interferon

Eight patients with basal cell carcinomas were treated with recombinant alpha-2 interferon. Each patient had a biopsy-proved basal cell carcinoma of the nodular or superficial type that was injected intralesionally three times a week for 3 weeks (9 total injections) with 1.5 X 10(6) IU (0.15 ml) of alpha-2 interferon per injection (total dose, 13.5 X 10(6) IU). Excisional biopsy 2 months after completion of therapy revealed no evidence of basal cell carcinoma in any patient. Minimal side effects were observed. In these eight patients alpha-2 interferon was therefore an effective and safe modality of treatment. The encouraging results of this pilot study suggest that additional evaluation of interferon in the treatment of basal cell carcinoma is warranted.

Intralesional interferon therapy for basal cell carcinoma

In a clinical trial of 172 patients at four medical centers, interferon alfa-2b (1.5 x 10(6) IU) or a placebo was injected directly into biopsy-proved noduloulcerative or superficial basal cell carcinomas three times weekly for 3 weeks, for a cumulative dose of 13.5 million IU. Efficacy of treatment was determined at 16 to 20 weeks by examination of biopsy specimens that demonstrated cure of lesions in 86% of interferon-treated patients and in only 29% of placebo-treated patients. During the treatment course and follow-up, an initial inflammatory response was observed at the treatment sites, followed by diminished erythema, improvement in overall appearance, and a decrease in size of lesions. Side effects of treatment, mainly flu-like symptoms, were usually mild and transient and occurred more commonly in the interferon-treated group. Only three patients, all in the interferon-treated group, discontinued therapy because of side effects. One year after initiation of therapy, 81% of interferon recipients and 20% of those given the placebo remained tumor free. Noduloulcerative and superficial lesions were equally responsive to treatment with interferon. For some patients with noduloulcerative or superficial basal cell carcinomas, intralesional interferon alfa-2b may be an alternative, effective treatment.

Mometasone furoate 0.1%—salicylic acid 5% ointment versus mometasone furoate 0.1% ointment in the treatment of moderate-to-severe psoriasis: a multicenter study

Topical corticosteroids and keratolytics are both used widely in the management of patients with psoriasis. A combination of the two types of agents may provide enhanced relief. The purpose of this study was to compare the efficacy and safety of the combination ointment mometasone furoate 0.1% plus salicylic acid 5% with that of mometasone furoate 0.1% ointment in the treatment of moderate-to-severe psoriasis vulgaris. A total of 408 patients were enrolled in this controlled, randomized, double-masked, parallel-group, multicenter comparison. Patients applied either mometasone furoate-salicylic acid ointment or mometasone furoate ointment alone to target lesions twice daily for 21 days. Severity of erythema, induration, and scaling were scored at baseline and at days 4, 8, 15, and 22. An evaluation of overall change in disease status of all treated lesions was performed at each follow-up visit. Adverse events were also monitored and scored, including signs of skin atrophy. Beginning on day 8, the combination of mometasone furoate-salicylic acid was significantly more effective than mometasone furoate alone, as indicated by the mean percentage of improvement in total disease scores, mean total disease sign scores, and the individual score for scaling. Similarly, the combination was more effective beginning on day 15, as indicated by the global evaluation of overall clinical response and individual scores for erythema and induration. Both treatments were well tolerated. Mometasone furoate-salicylic acid ointment provides more effective treatment of moderate-to-severe psoriasis than does mometasone furoate ointment alone and is safe and well tolerated.

Activity of Intralesional Interferon Alfa-2b in Viral and Malignant Skin Diseases

Interferon alfa-2b (Intron A®) is a highly purified single molecular species of alpha interferon and represents one of the more than twenty that exist naturally in man (1). It is produced using recombinant DNA techniques in the bacterium E. coli and is purified to a specific activity of approximately 2x100 IU/mg of protein. In common with the other alpha interferons, it has potent antiviral and antiproliferative properties when tested in vitro using human cell lines and viruses (2–4). Additionally, it causes the activation of natural killer cells (5), can restore cytotoxicity to functionally deficient monocytes (5), and like other alpha interferons would be expected to enhance antigen expression on cell surfaces (6). These properties suggested that interferon alfa-2b might have clinical utility in treating viral and malignant diseases in man. The ability to achieve high local concentrations in the skin by intralesional injection with comparatively little systemic exposure suggested further that malignant and premalignant skin diseases and those of a viral etiology might be especially amenable to treatment with interferon alfa-2b.