WAILEA, HAWAII – Moderate to severe psoriasis is an independent risk factor for a variety of adverse pregnancy outcomes, according to Dr. Jennifer C. Cather.
Yet much remains unknown about the impact of psoriasis and its treatment in pregnancy. For this reason, every psoriasis patient who becomes pregnant while on a biologic agent should be strongly encouraged to enter one of the pregnancy registries, Dr. Cather said at the Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation (SDEF).
She recommended the Organization of Teratology Information Specialists (OTIS), because the group helps inform concerned patients. OTIS operates pregnancy registries for women taking etanercept (Enbrel) or adalimumab (Humira). In addition, pharmaceutical companies that market biologics maintain pregnancy registries for their agents.
The Food and Drug Administration rates methotrexate and acitretin as pregnancy category X drugs and cyclosporine as a category C drug. The anti–tumor necrosis factor agents are category B – meaning animal studies have shown no fetal risk – as are alefacept (Amevive) and ustekinumab (Stelara).
"That doesn’t mean I think you should give a category B agent to people who are pregnant or are planning pregnancy, because I think that the best drug in pregnancy is probably no drug, or light treatment if you can get away with that," said Dr. Cather, who is in private practice in Dallas.
Still, there is sometimes no satisfactory alternative to using a biologic agent in pregnancy. Two of the toughest challenges Dr. Cather said she encounters in her clinical practice arise in such situations. One involves the psoriasis patient who calls and says that her ob.gyn. told her to come off the biologic therapy immediately.
The other challenge is the patient whose psoriasis worsens during pregnancy to the extent that she needs to start on a biologic agent or switch to another one. This is not an uncommon situation, Dr. Cather noted, citing a University of California, Irvine, study which found that while psoriasis improved during pregnancy in 55% of pregnant patients, it worsened in 23%. Postpartum, psoriasis worsened in 65% (Arch. Dermatol. 2005;141:601-6).
A recent retrospective matched cohort study of pregnancy outcomes in psoriasis patients involved 68 deliveries in 35 women with moderate to severe psoriasis and 237 deliveries in 236 controls in Israel.
The incidence of pregnancy-induced hypertensive diseases was 7.4% in the psoriasis patients, significantly greater than the 2.1% rate in controls. Premature rupture of membranes occurred in 16% of psoriasis patients, compared with 5.5% of controls. The 24% incidence of large-for-gestational-age newborns among the psoriasis patients’ babies was twice that of controls. Macrosomia occurred in 13% of the babies of women with psoriasis, compared with 4.2% of matched controls.
In this multivariate analysis, moderate to severe psoriasis was also an independent risk factor for previous spontaneous and induced abortions (J. Eur. Acad. Dermatol. Venereol. 2010 Nov. 25 doi: 10.1111/j.1468-3083.2010.03917.x]).
Dr. Cather’s biologics of choice for psoriasis and psoriatic arthritis, whether during pregnancy or not, are TNF-antagonists. She has been monitoring her own psoriasis patients who have been on biologic agents during pregnancy and has not noted any increase in adverse outcomes. While she finds this somewhat reassuring, the definitive answers will come from the large pregnancy registries.
Nursing mothers on methotrexate, acitretin, or cyclosporine should not breast-feed. The risk of using anti–tumor necrosis factor agents during breast-feeding is "probably negligible," she said.
Psoriasis patients have a below-average rate of childbearing. Theories abound as to why. Possibilities include an increased infertility rate, voluntary childlessness due to concern about genetic transmission of psoriasis to the next generation, and the interference with sexual activity that has been documented in patients with active disease.
"I do have people who say they never want to have children because of their disease. That’s a very sad conversation," Dr. Cather said.
Intriguingly, there is some recent evidence to suggest anti-TNF therapy may improve the results of in vitro fertilization in women with infertility and recurrent spontaneous abortion. The therapeutic rationale is that TNF-alpha has been shown to have antireproductive effects.
In a nonrandomized study involving 75 women without psoriasis under age 38 with Th1/Th2 cytokine elevation undergoing IVF for infertility, investigators found that implantation, clinical pregnancy, and live birth rates were significantly higher in those on adalimumab and IVIG than in patients on neither (Am. J. Repro. Immunol. 2009;61:113-20). This is a controversial study among assisted reproduction specialists, Dr. Cather noted.
She disclosed that she serves as a consultant to Amgen (manufacturer of Enbrel), Abbott (manufacturer of Humira), and Centocor (manufacturer of Stelara) and has received research grants from Amgen, Celgene, and Pfizer.