LAS VEGAS – To prevent immunogenicity to biologics, it’s best to have psoriasis patients on methotrexate at baseline, according to Dr. Bruce Strober of the University of Connecticut, Farmington.
Once patients develop antibodies to a biologic, “the horse is already out of the barn. It may be too late to recover efficacy by adding methotrexate,” Dr. Strober said. “Add the biologic to the methotrexate, not visa versa” (Br. J. Dermatol. 2012;167:649-57).
Dr. Bruce Strober
Anti–tumor necrosis factors and other biologics often lose their effects as patients build antibodies to the foreign proteins they contain. “Drug levels fall off a cliff when you have a lot of immunogenicity. The major challenge [is] making sure patients 1-3 years out see the response they got in the first 6 months,” Dr. Strober said at the SDEF Las Vegas Dermatology Seminar.
Methotrexate is thought to diminish the antibody response, blocking immunogenicity. “Biologics invariably show greater and more durable efficacy” with methotrexate “even when methotrexate is ineffective on its own,” he said. When oral therapy is indicated, Dr. Strober said he starts most of his psoriasis patients on about 15 mg/wk and waits 8-12 weeks to see whether this works. If there is no response, he will add a biologic and continue the methotrexate.
The dose of methotrexate needed to tame the antibody response remains unclear. “The consensus in the rheumatology world is somewhere around 15 mg weekly, but I don’t always use that dose. I will go down to 7.5 mg to 12.5 mg in many patients,” said Dr. Strober. “It appears anecdotally that there’s good protection of the [biologic] response with those doses. It’s something you might vary based on the size of the patient,” he said. “Episodic dosing gives you the greatest percent of patients getting antibodies, [so] dose biologics without interruption if you can,” he added (J. Am. Acad. Dermatol. 2007;56:31.e1-15).
Immunogenicity to one biologic does not necessarily translate to immunogenicity to another. Also, increasing infusion frequency can help recapture a biologic’s effect, he noted.
SDEF and this news organization are owned by Frontline Medical Communications. Dr. Strober is on the advisory board of or a consultant to several pharmaceutical companies, including Janssen, Abbott, Pfizer, and Amgen.