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A post hoc analysis of .
“Although contraception in female patients of childbearing age was mandatory before initiation of and during tildrakizumab therapy, some pregnancies occurred during the tildrakizumab clinical development program as protocol violations,” wrote Kathleen Haycraft, MD, of Riverside Dermatology & Spa, Hannibal, Mo., and colleagues.
Tildrakizumab (Ilumya), an interleukin-23 antagonist, was approved in 2018 by the Food and Drug Administration for treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy. Effects on birth outcomes or on neonates exposed during pregnancy have not been studied, the researchers said.
“Tildrakizumab plasma half-life after subcutaneous administration is approximately 25 days; therefore, tildrakizumab administered even in the first trimester may cross the placental barrier,” they noted.
In a research letter published in the British Journal of Dermatology, the investigators reviewed data from nine phase 1, 2, and 3 clinical trials and identified 528 women of childbearing age who received tildrakizumab. Fourteen pregnancies were reported among these women: six from a contraceptive failure, and eight for lack of contraception use. (One of the phase 1 trials was in patients with Crohn’s disease, which included one of the pregnancies; the rest were in patients with psoriasis.)
The 14 pregnancy outcomes included 2 spontaneous abortions (14.3%), 4 elective abortions (28.6%), and 8 live births (57.1%), which included 1 premature birth, with “no identifiable congenital anomalies,” the authors wrote. The longest duration of exposure to tildrakizumab in a pregnant woman was 1,196 days; this pregnancy resulted in a premature live birth at 36 weeks with no anomalies. The spontaneous abortion rate was similar to the rate in the general population, which is 12%-15%, the authors noted.
While the study “adds to the existing evidence on the outcomes of biologic treatment of psoriasis,” the findings were limited by several factors including the small number of pregnancies, short duration of exposure to tildrakizumab, variations in dosing, and lack of controls, the researchers noted. “Additional data from a larger population following tildrakizumab exposure are required to fully evaluate the safety and tolerability of tildrakizumab treatment during pregnancy,” they said. In the meantime, they advised women of childbearing age with psoriasis to continue to avoid pregnancy and follow practice guidelines for contraceptive use while taking the biologic therapy.
The studies were supported by Merck Sharp & Dohme, a Merck & Co. subsidiary; analyses were supported by Sun Pharmaceutical Industries. Lead author Dr. Haycraft disclosed relationships with companies including Sun, Celgene, Lilly, Novartis, Ortho-Derm, and Pfizer. Other authors disclosed relationships with Novartis, Celgene, Ortho Dermatologics, Janssen, and Merck; two authors are Sun employees.
dermnews@mdedge.com
SOURCE: Haycraft K et al. Br J Dermatol. 2020 Jan 29. doi: 10.1111/bjd.18897.
A post hoc analysis of .
“Although contraception in female patients of childbearing age was mandatory before initiation of and during tildrakizumab therapy, some pregnancies occurred during the tildrakizumab clinical development program as protocol violations,” wrote Kathleen Haycraft, MD, of Riverside Dermatology & Spa, Hannibal, Mo., and colleagues.
Tildrakizumab (Ilumya), an interleukin-23 antagonist, was approved in 2018 by the Food and Drug Administration for treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy. Effects on birth outcomes or on neonates exposed during pregnancy have not been studied, the researchers said.
“Tildrakizumab plasma half-life after subcutaneous administration is approximately 25 days; therefore, tildrakizumab administered even in the first trimester may cross the placental barrier,” they noted.
In a research letter published in the British Journal of Dermatology, the investigators reviewed data from nine phase 1, 2, and 3 clinical trials and identified 528 women of childbearing age who received tildrakizumab. Fourteen pregnancies were reported among these women: six from a contraceptive failure, and eight for lack of contraception use. (One of the phase 1 trials was in patients with Crohn’s disease, which included one of the pregnancies; the rest were in patients with psoriasis.)
The 14 pregnancy outcomes included 2 spontaneous abortions (14.3%), 4 elective abortions (28.6%), and 8 live births (57.1%), which included 1 premature birth, with “no identifiable congenital anomalies,” the authors wrote. The longest duration of exposure to tildrakizumab in a pregnant woman was 1,196 days; this pregnancy resulted in a premature live birth at 36 weeks with no anomalies. The spontaneous abortion rate was similar to the rate in the general population, which is 12%-15%, the authors noted.
While the study “adds to the existing evidence on the outcomes of biologic treatment of psoriasis,” the findings were limited by several factors including the small number of pregnancies, short duration of exposure to tildrakizumab, variations in dosing, and lack of controls, the researchers noted. “Additional data from a larger population following tildrakizumab exposure are required to fully evaluate the safety and tolerability of tildrakizumab treatment during pregnancy,” they said. In the meantime, they advised women of childbearing age with psoriasis to continue to avoid pregnancy and follow practice guidelines for contraceptive use while taking the biologic therapy.
The studies were supported by Merck Sharp & Dohme, a Merck & Co. subsidiary; analyses were supported by Sun Pharmaceutical Industries. Lead author Dr. Haycraft disclosed relationships with companies including Sun, Celgene, Lilly, Novartis, Ortho-Derm, and Pfizer. Other authors disclosed relationships with Novartis, Celgene, Ortho Dermatologics, Janssen, and Merck; two authors are Sun employees.
dermnews@mdedge.com
SOURCE: Haycraft K et al. Br J Dermatol. 2020 Jan 29. doi: 10.1111/bjd.18897.
A post hoc analysis of .
“Although contraception in female patients of childbearing age was mandatory before initiation of and during tildrakizumab therapy, some pregnancies occurred during the tildrakizumab clinical development program as protocol violations,” wrote Kathleen Haycraft, MD, of Riverside Dermatology & Spa, Hannibal, Mo., and colleagues.
Tildrakizumab (Ilumya), an interleukin-23 antagonist, was approved in 2018 by the Food and Drug Administration for treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy. Effects on birth outcomes or on neonates exposed during pregnancy have not been studied, the researchers said.
“Tildrakizumab plasma half-life after subcutaneous administration is approximately 25 days; therefore, tildrakizumab administered even in the first trimester may cross the placental barrier,” they noted.
In a research letter published in the British Journal of Dermatology, the investigators reviewed data from nine phase 1, 2, and 3 clinical trials and identified 528 women of childbearing age who received tildrakizumab. Fourteen pregnancies were reported among these women: six from a contraceptive failure, and eight for lack of contraception use. (One of the phase 1 trials was in patients with Crohn’s disease, which included one of the pregnancies; the rest were in patients with psoriasis.)
The 14 pregnancy outcomes included 2 spontaneous abortions (14.3%), 4 elective abortions (28.6%), and 8 live births (57.1%), which included 1 premature birth, with “no identifiable congenital anomalies,” the authors wrote. The longest duration of exposure to tildrakizumab in a pregnant woman was 1,196 days; this pregnancy resulted in a premature live birth at 36 weeks with no anomalies. The spontaneous abortion rate was similar to the rate in the general population, which is 12%-15%, the authors noted.
While the study “adds to the existing evidence on the outcomes of biologic treatment of psoriasis,” the findings were limited by several factors including the small number of pregnancies, short duration of exposure to tildrakizumab, variations in dosing, and lack of controls, the researchers noted. “Additional data from a larger population following tildrakizumab exposure are required to fully evaluate the safety and tolerability of tildrakizumab treatment during pregnancy,” they said. In the meantime, they advised women of childbearing age with psoriasis to continue to avoid pregnancy and follow practice guidelines for contraceptive use while taking the biologic therapy.
The studies were supported by Merck Sharp & Dohme, a Merck & Co. subsidiary; analyses were supported by Sun Pharmaceutical Industries. Lead author Dr. Haycraft disclosed relationships with companies including Sun, Celgene, Lilly, Novartis, Ortho-Derm, and Pfizer. Other authors disclosed relationships with Novartis, Celgene, Ortho Dermatologics, Janssen, and Merck; two authors are Sun employees.
dermnews@mdedge.com
SOURCE: Haycraft K et al. Br J Dermatol. 2020 Jan 29. doi: 10.1111/bjd.18897.
FROM THE BRITISH JOURNAL OF DERMATOLOGY