NEW ORLEANS – Topical immunomodulators did not increase overall risk for lymphoma in a large retrospective study of patients with atopic dermatitis.
Researchers identified 760 cases of lymphoma in a claims database of 625,915 atopic patients. They assessed risk of lymphoma associated with pimecrolimus cream 1%, tacrolimus ointment 0.1% or 0.3%, and topical corticosteroid treatment, compared with patients not treated with the agents. They also looked at a group of 3,040 atopic dermatitis patients to control for age and gender in each lymphoma case.
"This study found no increased risk of overall lymphoma in atopic dermatitis patients treated with topical corticosteroids or topical calcineurin inhibitors," said Dr. Alejandro Arana, a researcher in Zaragoza, Spain.
Compared with lymphoma risk in the control group of atopic dermatitis patients who did not use any of the agents in the study (odds ratio, 1), risk was lower with pimecrolimus (OR, 0.76) and topical corticosteroids (OR, 0.90). In contrast, risk was increased for patients treated with tacrolimus (OR, 1.24).
"The lower risk of lymphoma appears to be reassuring," said session moderator Dr. Jan Izakovic, a dermatologist at the University of Miami.
Because of specific concerns about elevated risk for lymphoma associated with topical immunomodulators in children and adolescents, Dr. Arana and his associates separately assessed the 186 atopic patients with lymphoma and 741 atopic controls younger than 20 years.
"The results were similar," said Dr. Arana.
In the younger population 186 atopic patients with lymphoma and 741 atopic controls all risks for lymphoma were lower: with pimecrolimus (OR, 0.64); topical corticosteroids (OR, 0.72); and tacrolimus (OR, 0.96).
"Among those younger than 20, we feel very reassured," Dr. Arana said. "We didn’t find any risk."
All atopic dermatitis and lymphoma cases were identified using ICD-9 codes in the PharMetrics Integrated Database between July 1995 and March 2009. Mean age was 38 years, and 43% of patients were male.
The researchers also looked at subtypes of lymphoma. Of the 760 cases, 106 were Hodgkin's lymphoma. The 200 cases of non-Hodgkin's lymphoma included 118 T-cell lymphomas, 30 B-cell lymphomas, and 52 indeterminate types. The remaining 454 cases (60%) were not classified by subtype, a potential limitation of the study.
"We also looked at exposure to immunomodulators and risk of T-cell lymphoma, the subtype we are most concerned about," Dr. Arana said.
Dr. Arana and his associates assessed this risk in patients of all ages. Compared with a reference group of 45 cases with T-cell lymphoma and 228 controls not exposed to any of the medications (OR, 1.0), risk was lower with pimecrolimus (OR, 0.85); slightly increased with corticosteroids (OR, 1.16); and greater with tacrolimus (OR, 4.95).
"We should be very, very careful with these results," Dr. Arana said. The results are only suggestive, he added, because of the small number of cases of T-cell lymphoma, and the researchers' inability to determine lymphoma subtype in a majority of cases. In addition, cases with more severe atopic dermatitis could have confounded the results.
Nevertheless, the study size was sufficient to precisely estimate the association between overall lymphoma risk and use of topical calcineurin inhibitors, Dr. Arana said.
The researchers also looked at overall risk of lymphoma in all patients by dose. For example, they looked at pimecrolimus doses less than 0.3 g; 0.3 g to less than 0.6 g; 0.6 g to less than 1.0 g; and 1.0 g or greater. They also looked at tacrolimus doses of less than 0.03 g; 0.03 g to less than 0.06 g; 0.06 g to less than 0.10 g; and 0.10 g or greater.
"We didn't see any dose response for any corticosteroids or pimecrolimus, and a slightly increased risk for tacrolimus of 0.10 g or greater, with an odds ratio of 2.08," Dr. Arana said.
The study was funded through an unrestricted grant from Novartis. Dr. Arana had no relevant disclosures, but said two of the study coauthors are Novartis employees.