KAUAI, HAWAII – When certolizumab pegol receives marketing approval for moderate to severe psoriasis – which experts say is a virtual lock – it will offer a singular advantage over current anti–tumor necrosis factor (anti-TNF) biologics: strong evidence of safety in pregnancy.
“” Kenneth B. Gordon, MD, observed at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation. (Cimzia) is approved for use in psoriatic arthritis, rheumatoid arthritis, ankylosing spondylitis, and Crohn’s disease. Prescribing certolizumab for psoriasis is currently an off-label use, but the biologic is currently under review by the Food and Drug Administration and European regulators for an expanded indication in adults with chronic moderate to severe plaque psoriasis.
Lots of women and their families are understandably deeply concerned about using powerful, transformative medications during pregnancy, even though they know from experience how debilitating inadequately treated psoriasis can be.
“Many women of childbearing potential would find [certolizumab] to be a preferential agent if they’re planning to become pregnant,” said, professor and chair of the department of dermatology at the Medical College of Wisconsin, Milwaukee.
He cited the CRIB (A Multicenter, Postmarketing Study Evaluating the Transfer of Cimzia From the Mother to the Infant via the Placenta) study results presented by, at the 2017 annual meeting of the European Academy of Dermatology and Venereology in Geneva as a major step forward in establishing the safety of certolizumab during pregnancy.
was a prospective postmarketing pharmacokinetic study that evaluated placental transfer of certolizumab from 16 pregnant women on the biologic to their infants. All of the mothers received their last dose of certolizumab for rheumatoid arthritis or other approved indications within 35 days of delivery. Blood samples were collected from mothers, newborns, and umbilical cords within 1 hour of delivery, and again from the infants at weeks 4 and 8 after delivery.
Only one infant had a detectable plasma level of certolizumab at birth, and it was barely measurable at 0.042 mcg/mL, as compared with 49.4 mcg/mL in the mother’s plasma. This is consistent with the fact that certolizumab’s pegylated arm allows only minimal or no placental transfer from mother to infant, so there is essentially no third trimester in utero fetal exposure. In contrast, as Dr. Kimball noted, other anti-TNF biologics lack a pegylated arm and thus preferentially cross the placenta, creating a theoretical increased risk of maternal pregnancy complications and/or congenital malformations.
Dr. Kimball, professor of dermatology at Harvard Medical School and chief executive officer of Harvard Medical Faculty Physicians at Beth Israel Deaconess Medical Center, both in Boston, also has been deeply involved in an ongoing registry (sponsored by certolizumab manufacturer UCB) of several hundred women on certolizumab in pregnancy. The data have reassuringly shown no increased risk of maternal pregnancy complications such as preeclampsia, gestational diabetes, or preterm birth, nor any increase in or pattern of congenital malformations, compared with background rates in the general population.
Dr. Gordon said that while he understands the concerns, he personally doesn’t think the class-wide safety of TNF inhibitors in pregnancy and lactation is a big issue.
“My argument is that anti-TNF agents have been used very frequently in women of childbearing age, and also in women who are pregnant or lactating. And there have not been any side effect signals from that,” he explained.
The prospects of gaining an expanded indication for certolizumab in psoriasis hinge in part on the impressive results of the pivotal phase 3, randomized, double-blind, placebo-controlledand trials. In CIMPASI-1, the week-48 Psoriasis Area and Severity Index (PASI) 75 and PASI 90 response rates were 87.1% and 60.2%, respectively, in patients on the biologic at 400 mg every 2 weeks; among those on certolizumab at 200 mg every 2 weeks, the rates were 67.2% and 42.8%. In CIMPASI-2, the PASI 75 and PASI 90 rates were 81.3% and 62.0% at 400 mg and 78.7% and 59.6% with 200 mg every 2 weeks.
There were no cases of tuberculosis or any other significant safety concerns through 48 weeks, Dr. Gordon said.
“Certolizumab is coming soon for psoriasis,” predicted Craig L. Leonardi, MD, a psoriasis researcher at Saint Louis University. “The data are very impressive. It’s a high-performance drug. There’s no reason why this drug shouldn’t be approved.”
Since Dr. Kimball’s presentation of the CRIB data at the 2017 annual meeting of the European Academy of Dermatology and Venereology, the study has been published ().
Dr. Gordon reported receiving research support from and serving as a paid consultant to numerous pharmaceutical companies developing new psoriasis therapies.
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