Treatment of Psoriasis in Pregnancy

Article Type
Article
Changed
Thu, 11/03/2022 - 22:12
Author(s)
Kelsey S. Flood, MD
Kevin T. Savage, MD
Martina L. Porter, MD
Alexa B. Kimball, MD, MPH

Historically, there have been limited data available on the management of psoriasis in pregnancy. The most comprehensive discussion of treatment guidelines is from 2012.1 In the interim, many biologics have been approved for treating psoriasis, with slow accumulation of pregnancy safety data. The 2019 American Academy of Dermatology–National Psoriasis Foundation guidelines on biologics for psoriasis contain updated information but also highlight the paucity of pregnancy safety data.2 This gap is in part a consequence of the exclusion and disenrollment of pregnant women from clinical trials.3 Additionally, lack of detection through registries contributes; pregnancy capture in registries is low compared to the expected number of pregnancies estimated from US Census data.4 Despite these shortcomings, psoriasis patients who are already pregnant or are considering becoming pregnant frequently are encountered in practice and may need treatment. This article reviews the evidence on commonly used treatments for psoriasis in pregnancy.

Background

For many patients, psoriasis improves during pregnancy5,6 and becomes worse postpartum. In a prospective study, most patients reported improvement in pregnancy corresponding to a significant decrease in affected body surface area (P<.001) by 10 to 20 weeks’ gestation. Most patients also reported worsening of psoriasis postpartum; a significant increase in psoriatic body surface area (P=.001) was observed after delivery.7 Despite these findings, a considerable number of patients also experience stable disease or worsening of disease during pregnancy.

In addition to the maternal disease state, the issue of pregnancy outcomes is paramount. In the inflammatory bowel disease and rheumatology literature, it is established that uncontrolled disease is associated with poorer pregnancy outcomes.8-10 Guidelines vary among societies on the use of biologics in pregnancy generally (eTable 11,2,9,11-24), but some societies recommend systemic agents to achieve disease control during pregnancy.9,25

Assessing the potential interplay between disease severity and outcomes in pregnant women with psoriasis is further complicated by the slowly growing body of literature demonstrating that women with psoriasis have more comorbidities26 and worse pregnancy outcomes.27,28 Pregnant psoriasis patients are more likely to smoke, have depression, and be overweight or obese prior to pregnancy and are less likely to take prenatal vitamins.26 They also have an increased risk for cesarean birth, gestational diabetes, gestational hypertension, and preeclampsia.28 In contrast to these prior studies, a systematic review revealed no risk for adverse outcomes in pregnant women with psoriasis.29

Assessment of Treatments for Psoriasis in Pregnancy

In light of these issues, treatment of psoriasis during pregnancy should be assessed from several vantage points. Of note, the US Food and Drug Administration changed its classification scheme in 2015 to a more narrative format called the Pregnancy and Lactation Labeling Rule.30 Prior classifications, however, provide a reasonable starting point for categorizing the safety of drugs (Table31). Importantly, time of exposure to systemic agents also matters; first-trimester exposure is more likely to affect embryogenesis, whereas second- and third-trimester exposures are more prone to affect other aspects of fetal growth. eTable 2 provides data on the use of oral and topical medications to treat psoriasis in pregnancy.1,8,22,32-45

Topical Agents
Topical steroids are largely understood to be reasonable treatment options, though consideration of potency, formulation, area of application, and use of occlusion is important.1,46 Risk for orofacial cleft has been noted with first-trimester topical steroid exposure, though a 2015 Cochrane review update determined that the relative risk of this association was not significantly elevated.32



The impact of topical calcipotriene and salicylic acid has not been studied in human pregnancies,1 but systemic absorption can occur for both. There is potential for vitamin D toxicity with calcipotriene46; consequently, use during pregnancy is not recommended.1,46 Some authors recommend against topical salicylic acid in pregnancy; others report that limited exposure is permissible.47 In fact, as salicylic acid commonly is found in over-the-counter acne products, many women of childbearing potential likely have quotidian exposure.

Preterm delivery and low birthweight have been reported with oral tacrolimus; however, risk with topical tacrolimus is thought to be low1 because the molecular size likely prohibits notable absorption.47 Evidence for the use of anthralin and coal tar also is scarce. First-trimester coal tar use should be avoided; subsequent use in pregnancy should be restricted given concern for adverse outcomes.1

 

 



Phototherapy
Broadband or narrowband UVB therapy is recommended as second-line therapy in pregnancy. No cases of fetal risk or premature delivery associated with UVB therapy were found in our search.1 Phototherapy can exacerbate melasma47 and decrease folate levels48; as such, some authors recommend folate supplementation in females of childbearing age who are being treated with phototherapy.49 Psoralen, used in psoralen plus UVA therapy, is mutagenic and therefore contraindicated in pregnancy.1

Oral Medications
Both methotrexate, which is a teratogen, abortifacient, and mutagen,1 and systemic retinoids, which are teratogens, are contraindicated in pregnancy.1,47 Acitretin labeling recommends avoiding pregnancy for 3 years posttreatment50 because alcohol intake prolongs the medication’s half-life.22



Apremilast use is not documented in pregnant psoriasis patients51; an ongoing registry of the Organization of Tetralogy Information Specialists has not reported publicly to date.52 Animal studies of apremilast have documented dose-related decreased birthweight and fetal loss.22

Safety data for systemic steroids, used infrequently in psoriasis, are not well established. First-trimester prednisone exposure has been associated with prematurity, low birthweight, and congenital abnormalities.38 A separate evaluation of 1047 children exposed to betamethasone in utero failed to demonstrate significant change in birthweight or head circumference. However, repeat antenatal corticosteroid exposure was associated with attention problems at 2 years of age.39

Data regarding cyclosporine use, derived primarily from organ transplant recipients, suggest elevated risk for prematurity and low birthweight.53,54 A meta-analysis demonstrated that organ transplant recipients taking cyclosporine had a nonsignificantly elevated odds ratio for congenital malformations, prematurity, and low birthweight.42 Cyclosporine use for psoriasis in pregnancy is not well described; in a study, rates of prematurity and low birthweight were both 21%.43 Limited data are available for Janus kinase inhibitors, none of which are approved for psoriasis, though clinical trials in psoriasis and psoriatic arthritis are underway (ClinicalTrials.gov identifiers NCT04246372, NCT03104374, NCT03104400).

Biologics and Small-Molecule Inhibitors
Limited data on biologics in pregnancy exist25 (eTable 3). Placental transport of IgG antibodies, including biologics, increases throughout pregnancy, especially in the third trimester.82 Infants of mothers treated with a biologic with potential for placental transfer are therefore considered by some authors to be immunosuppressed during the first months of life.2

Looking globally across biologics used for psoriasis, limited safety data are encouraging. In a review of PSOLAR (Psoriasis Longitudinal Assessment and Registry), 83 pregnancies with biologic exposure resulted in 59 live births (71%); 18 spontaneous abortions (22%); 6 induced abortions (7%); no congenital abnormalities; and 7 reports of neonatal problems, including respiratory issues, ABO blood group mismatch, hospitalization, and opioid withdrawal.83

Use of tumor necrosis factor (TNF) inhibitors in pregnancy has the most data25 and is considered a reasonable treatment option. Historically, there was concern about the risk for VACTERL syndrome (vertebral defects, anal atresia, cardiac defects, tracheoesophageal fistula, renal anomalies, limb abnormalities) with exposure to a TNF inhibitor,25,84-86 but further reports have alleviated these concerns. Active transplacental transport occurs for adalimumab, infliximab, and golimumab,87 but given structural differences, transport of certolizumab and etanercept is substantially less.88,89 In the CRIB study of placental transfer of certolizumab from mother to infant (N=14), pharmacokinetic data demonstrated no quantifiable certolizumab levels in 13 infants and minimal levels in 1 infant at birth.88 There are fewer data available on the use of other biologics in pregnancy, but for those in which active placental transport is relevant, similar concerns (ie, immunosuppression) might arise (eTable 3).

Concern over biologics largely involves risk for newborn immunosuppression. A case report detailed a Crohn disease patient treated with infliximab who gave birth to an infant who died of disseminated bacille Calmette-Guérin infection at 4.5 months after receiving the vaccine at 3 months.90 This case underscores the importance of delaying live vaccination in infants born to mothers who were treated with a biologic during pregnancy. Authors have provided various data on how long to avoid vaccination; some state as long as 1 year.91

In pregnant females with inflammatory bowel disease treated with a biologic, no correlation was observed among maternal, placental, and infant serum biologic levels and neonatal infection. However, an association between preterm birth and the level of the biologic in maternal and placental (but not infant) serum and preterm birth was observed.92



In another report from the same registry, combination therapy with a TNF inhibitor and another immunomodulator led to an increased risk for infection in infants at 12 months of age, compared to infants exposed to monotherapy89 or exposed to neither agent.93 A strategy to circumvent this potential problem is to avoid treatment with actively transported molecules in the third trimester.

Conclusion

Limited data exist to guide providers who are treating pregnant women with psoriasis. Our understanding of treatment of psoriasis in pregnancy is limited as a consequence of regulations surrounding clinical trials and inadequate detection of pregnancies in registries. Further efforts are necessary to better understand the relationship between psoriasis and pregnancy and how to manage pregnant women with psoriasis.

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Author and Disclosure Information

Dr. Flood is from the Department of Dermatology, University of Cincinnati, Ohio. Drs. Savage, Porter, and Kimball are from Beth Israel Deaconess Medical Center, Boston, Massachusetts. Drs. Porter and Kimball are from the Clinical Laboratory for Epidemiology and Applied Research in Skin (CLEARS), Department of Dermatology.

Dr. Flood has received fellowship funding from AbbVie; Janssen Biotech, Inc; and the National Psoriasis Foundation that went directly to her institution. Dr. Savage reports no conflict of interest. Dr. Porter is a consultant and/or investigator for AbbVie; Bristol-Myers Squibb; Eli Lilly and Company; Janssen Biotech, Inc; Novartis; Pfizer; and UCB. She gave a talk on psoriasis and pregnancy for an honorarium for the National Psoriasis Foundation. Dr. Kimball is a consultant and investigator for AbbVie; Bristol-Myers Squibb; Eli Lilly and Company; Janssen Biotech, Inc; Novartis; Pfizer Inc; and UCB. She serves on the University of California, San Diego, OTIS (Organization of Teratology Information Specialists) Pregnancy Study Scientific Advisory Panels for the Apremilast Pregnancy Exposure Registry (Amgen Inc) and the Ustekinumab Pregnancy Exposure Registry (Janssen Biotech, Inc). Her fellowship program receives funding from AbbVie; Janssen Biotech, Inc; and the National Psoriasis Foundation.

The eTables are available in the Appendix online at www.mdedge.com/dermatology.

Correspondence: Alexa B. Kimball, MD, MPH, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA 02215 (Clears@bidmc.harvard.edu).

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Author(s)
Kelsey S. Flood, MD
Kevin T. Savage, MD
Martina L. Porter, MD
Alexa B. Kimball, MD, MPH
Author(s)
Kelsey S. Flood, MD
Kevin T. Savage, MD
Martina L. Porter, MD
Alexa B. Kimball, MD, MPH
Author and Disclosure Information

Dr. Flood is from the Department of Dermatology, University of Cincinnati, Ohio. Drs. Savage, Porter, and Kimball are from Beth Israel Deaconess Medical Center, Boston, Massachusetts. Drs. Porter and Kimball are from the Clinical Laboratory for Epidemiology and Applied Research in Skin (CLEARS), Department of Dermatology.

Dr. Flood has received fellowship funding from AbbVie; Janssen Biotech, Inc; and the National Psoriasis Foundation that went directly to her institution. Dr. Savage reports no conflict of interest. Dr. Porter is a consultant and/or investigator for AbbVie; Bristol-Myers Squibb; Eli Lilly and Company; Janssen Biotech, Inc; Novartis; Pfizer; and UCB. She gave a talk on psoriasis and pregnancy for an honorarium for the National Psoriasis Foundation. Dr. Kimball is a consultant and investigator for AbbVie; Bristol-Myers Squibb; Eli Lilly and Company; Janssen Biotech, Inc; Novartis; Pfizer Inc; and UCB. She serves on the University of California, San Diego, OTIS (Organization of Teratology Information Specialists) Pregnancy Study Scientific Advisory Panels for the Apremilast Pregnancy Exposure Registry (Amgen Inc) and the Ustekinumab Pregnancy Exposure Registry (Janssen Biotech, Inc). Her fellowship program receives funding from AbbVie; Janssen Biotech, Inc; and the National Psoriasis Foundation.

The eTables are available in the Appendix online at www.mdedge.com/dermatology.

Correspondence: Alexa B. Kimball, MD, MPH, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA 02215 (Clears@bidmc.harvard.edu).

Author and Disclosure Information

Dr. Flood is from the Department of Dermatology, University of Cincinnati, Ohio. Drs. Savage, Porter, and Kimball are from Beth Israel Deaconess Medical Center, Boston, Massachusetts. Drs. Porter and Kimball are from the Clinical Laboratory for Epidemiology and Applied Research in Skin (CLEARS), Department of Dermatology.

Dr. Flood has received fellowship funding from AbbVie; Janssen Biotech, Inc; and the National Psoriasis Foundation that went directly to her institution. Dr. Savage reports no conflict of interest. Dr. Porter is a consultant and/or investigator for AbbVie; Bristol-Myers Squibb; Eli Lilly and Company; Janssen Biotech, Inc; Novartis; Pfizer; and UCB. She gave a talk on psoriasis and pregnancy for an honorarium for the National Psoriasis Foundation. Dr. Kimball is a consultant and investigator for AbbVie; Bristol-Myers Squibb; Eli Lilly and Company; Janssen Biotech, Inc; Novartis; Pfizer Inc; and UCB. She serves on the University of California, San Diego, OTIS (Organization of Teratology Information Specialists) Pregnancy Study Scientific Advisory Panels for the Apremilast Pregnancy Exposure Registry (Amgen Inc) and the Ustekinumab Pregnancy Exposure Registry (Janssen Biotech, Inc). Her fellowship program receives funding from AbbVie; Janssen Biotech, Inc; and the National Psoriasis Foundation.

The eTables are available in the Appendix online at www.mdedge.com/dermatology.

Correspondence: Alexa B. Kimball, MD, MPH, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA 02215 (Clears@bidmc.harvard.edu).

Article PDF
CT106002015_SI.PDF
Article PDF
CT106002015_SI.PDF

Historically, there have been limited data available on the management of psoriasis in pregnancy. The most comprehensive discussion of treatment guidelines is from 2012.1 In the interim, many biologics have been approved for treating psoriasis, with slow accumulation of pregnancy safety data. The 2019 American Academy of Dermatology–National Psoriasis Foundation guidelines on biologics for psoriasis contain updated information but also highlight the paucity of pregnancy safety data.2 This gap is in part a consequence of the exclusion and disenrollment of pregnant women from clinical trials.3 Additionally, lack of detection through registries contributes; pregnancy capture in registries is low compared to the expected number of pregnancies estimated from US Census data.4 Despite these shortcomings, psoriasis patients who are already pregnant or are considering becoming pregnant frequently are encountered in practice and may need treatment. This article reviews the evidence on commonly used treatments for psoriasis in pregnancy.

Background

For many patients, psoriasis improves during pregnancy5,6 and becomes worse postpartum. In a prospective study, most patients reported improvement in pregnancy corresponding to a significant decrease in affected body surface area (P<.001) by 10 to 20 weeks’ gestation. Most patients also reported worsening of psoriasis postpartum; a significant increase in psoriatic body surface area (P=.001) was observed after delivery.7 Despite these findings, a considerable number of patients also experience stable disease or worsening of disease during pregnancy.

In addition to the maternal disease state, the issue of pregnancy outcomes is paramount. In the inflammatory bowel disease and rheumatology literature, it is established that uncontrolled disease is associated with poorer pregnancy outcomes.8-10 Guidelines vary among societies on the use of biologics in pregnancy generally (eTable 11,2,9,11-24), but some societies recommend systemic agents to achieve disease control during pregnancy.9,25

Assessing the potential interplay between disease severity and outcomes in pregnant women with psoriasis is further complicated by the slowly growing body of literature demonstrating that women with psoriasis have more comorbidities26 and worse pregnancy outcomes.27,28 Pregnant psoriasis patients are more likely to smoke, have depression, and be overweight or obese prior to pregnancy and are less likely to take prenatal vitamins.26 They also have an increased risk for cesarean birth, gestational diabetes, gestational hypertension, and preeclampsia.28 In contrast to these prior studies, a systematic review revealed no risk for adverse outcomes in pregnant women with psoriasis.29

Assessment of Treatments for Psoriasis in Pregnancy

In light of these issues, treatment of psoriasis during pregnancy should be assessed from several vantage points. Of note, the US Food and Drug Administration changed its classification scheme in 2015 to a more narrative format called the Pregnancy and Lactation Labeling Rule.30 Prior classifications, however, provide a reasonable starting point for categorizing the safety of drugs (Table31). Importantly, time of exposure to systemic agents also matters; first-trimester exposure is more likely to affect embryogenesis, whereas second- and third-trimester exposures are more prone to affect other aspects of fetal growth. eTable 2 provides data on the use of oral and topical medications to treat psoriasis in pregnancy.1,8,22,32-45

Topical Agents
Topical steroids are largely understood to be reasonable treatment options, though consideration of potency, formulation, area of application, and use of occlusion is important.1,46 Risk for orofacial cleft has been noted with first-trimester topical steroid exposure, though a 2015 Cochrane review update determined that the relative risk of this association was not significantly elevated.32



The impact of topical calcipotriene and salicylic acid has not been studied in human pregnancies,1 but systemic absorption can occur for both. There is potential for vitamin D toxicity with calcipotriene46; consequently, use during pregnancy is not recommended.1,46 Some authors recommend against topical salicylic acid in pregnancy; others report that limited exposure is permissible.47 In fact, as salicylic acid commonly is found in over-the-counter acne products, many women of childbearing potential likely have quotidian exposure.

Preterm delivery and low birthweight have been reported with oral tacrolimus; however, risk with topical tacrolimus is thought to be low1 because the molecular size likely prohibits notable absorption.47 Evidence for the use of anthralin and coal tar also is scarce. First-trimester coal tar use should be avoided; subsequent use in pregnancy should be restricted given concern for adverse outcomes.1

 

 



Phototherapy
Broadband or narrowband UVB therapy is recommended as second-line therapy in pregnancy. No cases of fetal risk or premature delivery associated with UVB therapy were found in our search.1 Phototherapy can exacerbate melasma47 and decrease folate levels48; as such, some authors recommend folate supplementation in females of childbearing age who are being treated with phototherapy.49 Psoralen, used in psoralen plus UVA therapy, is mutagenic and therefore contraindicated in pregnancy.1

Oral Medications
Both methotrexate, which is a teratogen, abortifacient, and mutagen,1 and systemic retinoids, which are teratogens, are contraindicated in pregnancy.1,47 Acitretin labeling recommends avoiding pregnancy for 3 years posttreatment50 because alcohol intake prolongs the medication’s half-life.22



Apremilast use is not documented in pregnant psoriasis patients51; an ongoing registry of the Organization of Tetralogy Information Specialists has not reported publicly to date.52 Animal studies of apremilast have documented dose-related decreased birthweight and fetal loss.22

Safety data for systemic steroids, used infrequently in psoriasis, are not well established. First-trimester prednisone exposure has been associated with prematurity, low birthweight, and congenital abnormalities.38 A separate evaluation of 1047 children exposed to betamethasone in utero failed to demonstrate significant change in birthweight or head circumference. However, repeat antenatal corticosteroid exposure was associated with attention problems at 2 years of age.39

Data regarding cyclosporine use, derived primarily from organ transplant recipients, suggest elevated risk for prematurity and low birthweight.53,54 A meta-analysis demonstrated that organ transplant recipients taking cyclosporine had a nonsignificantly elevated odds ratio for congenital malformations, prematurity, and low birthweight.42 Cyclosporine use for psoriasis in pregnancy is not well described; in a study, rates of prematurity and low birthweight were both 21%.43 Limited data are available for Janus kinase inhibitors, none of which are approved for psoriasis, though clinical trials in psoriasis and psoriatic arthritis are underway (ClinicalTrials.gov identifiers NCT04246372, NCT03104374, NCT03104400).

Biologics and Small-Molecule Inhibitors
Limited data on biologics in pregnancy exist25 (eTable 3). Placental transport of IgG antibodies, including biologics, increases throughout pregnancy, especially in the third trimester.82 Infants of mothers treated with a biologic with potential for placental transfer are therefore considered by some authors to be immunosuppressed during the first months of life.2

Looking globally across biologics used for psoriasis, limited safety data are encouraging. In a review of PSOLAR (Psoriasis Longitudinal Assessment and Registry), 83 pregnancies with biologic exposure resulted in 59 live births (71%); 18 spontaneous abortions (22%); 6 induced abortions (7%); no congenital abnormalities; and 7 reports of neonatal problems, including respiratory issues, ABO blood group mismatch, hospitalization, and opioid withdrawal.83

Use of tumor necrosis factor (TNF) inhibitors in pregnancy has the most data25 and is considered a reasonable treatment option. Historically, there was concern about the risk for VACTERL syndrome (vertebral defects, anal atresia, cardiac defects, tracheoesophageal fistula, renal anomalies, limb abnormalities) with exposure to a TNF inhibitor,25,84-86 but further reports have alleviated these concerns. Active transplacental transport occurs for adalimumab, infliximab, and golimumab,87 but given structural differences, transport of certolizumab and etanercept is substantially less.88,89 In the CRIB study of placental transfer of certolizumab from mother to infant (N=14), pharmacokinetic data demonstrated no quantifiable certolizumab levels in 13 infants and minimal levels in 1 infant at birth.88 There are fewer data available on the use of other biologics in pregnancy, but for those in which active placental transport is relevant, similar concerns (ie, immunosuppression) might arise (eTable 3).

Concern over biologics largely involves risk for newborn immunosuppression. A case report detailed a Crohn disease patient treated with infliximab who gave birth to an infant who died of disseminated bacille Calmette-Guérin infection at 4.5 months after receiving the vaccine at 3 months.90 This case underscores the importance of delaying live vaccination in infants born to mothers who were treated with a biologic during pregnancy. Authors have provided various data on how long to avoid vaccination; some state as long as 1 year.91

In pregnant females with inflammatory bowel disease treated with a biologic, no correlation was observed among maternal, placental, and infant serum biologic levels and neonatal infection. However, an association between preterm birth and the level of the biologic in maternal and placental (but not infant) serum and preterm birth was observed.92



In another report from the same registry, combination therapy with a TNF inhibitor and another immunomodulator led to an increased risk for infection in infants at 12 months of age, compared to infants exposed to monotherapy89 or exposed to neither agent.93 A strategy to circumvent this potential problem is to avoid treatment with actively transported molecules in the third trimester.

Conclusion

Limited data exist to guide providers who are treating pregnant women with psoriasis. Our understanding of treatment of psoriasis in pregnancy is limited as a consequence of regulations surrounding clinical trials and inadequate detection of pregnancies in registries. Further efforts are necessary to better understand the relationship between psoriasis and pregnancy and how to manage pregnant women with psoriasis.

Historically, there have been limited data available on the management of psoriasis in pregnancy. The most comprehensive discussion of treatment guidelines is from 2012.1 In the interim, many biologics have been approved for treating psoriasis, with slow accumulation of pregnancy safety data. The 2019 American Academy of Dermatology–National Psoriasis Foundation guidelines on biologics for psoriasis contain updated information but also highlight the paucity of pregnancy safety data.2 This gap is in part a consequence of the exclusion and disenrollment of pregnant women from clinical trials.3 Additionally, lack of detection through registries contributes; pregnancy capture in registries is low compared to the expected number of pregnancies estimated from US Census data.4 Despite these shortcomings, psoriasis patients who are already pregnant or are considering becoming pregnant frequently are encountered in practice and may need treatment. This article reviews the evidence on commonly used treatments for psoriasis in pregnancy.

Background

For many patients, psoriasis improves during pregnancy5,6 and becomes worse postpartum. In a prospective study, most patients reported improvement in pregnancy corresponding to a significant decrease in affected body surface area (P<.001) by 10 to 20 weeks’ gestation. Most patients also reported worsening of psoriasis postpartum; a significant increase in psoriatic body surface area (P=.001) was observed after delivery.7 Despite these findings, a considerable number of patients also experience stable disease or worsening of disease during pregnancy.

In addition to the maternal disease state, the issue of pregnancy outcomes is paramount. In the inflammatory bowel disease and rheumatology literature, it is established that uncontrolled disease is associated with poorer pregnancy outcomes.8-10 Guidelines vary among societies on the use of biologics in pregnancy generally (eTable 11,2,9,11-24), but some societies recommend systemic agents to achieve disease control during pregnancy.9,25

Assessing the potential interplay between disease severity and outcomes in pregnant women with psoriasis is further complicated by the slowly growing body of literature demonstrating that women with psoriasis have more comorbidities26 and worse pregnancy outcomes.27,28 Pregnant psoriasis patients are more likely to smoke, have depression, and be overweight or obese prior to pregnancy and are less likely to take prenatal vitamins.26 They also have an increased risk for cesarean birth, gestational diabetes, gestational hypertension, and preeclampsia.28 In contrast to these prior studies, a systematic review revealed no risk for adverse outcomes in pregnant women with psoriasis.29

Assessment of Treatments for Psoriasis in Pregnancy

In light of these issues, treatment of psoriasis during pregnancy should be assessed from several vantage points. Of note, the US Food and Drug Administration changed its classification scheme in 2015 to a more narrative format called the Pregnancy and Lactation Labeling Rule.30 Prior classifications, however, provide a reasonable starting point for categorizing the safety of drugs (Table31). Importantly, time of exposure to systemic agents also matters; first-trimester exposure is more likely to affect embryogenesis, whereas second- and third-trimester exposures are more prone to affect other aspects of fetal growth. eTable 2 provides data on the use of oral and topical medications to treat psoriasis in pregnancy.1,8,22,32-45

Topical Agents
Topical steroids are largely understood to be reasonable treatment options, though consideration of potency, formulation, area of application, and use of occlusion is important.1,46 Risk for orofacial cleft has been noted with first-trimester topical steroid exposure, though a 2015 Cochrane review update determined that the relative risk of this association was not significantly elevated.32



The impact of topical calcipotriene and salicylic acid has not been studied in human pregnancies,1 but systemic absorption can occur for both. There is potential for vitamin D toxicity with calcipotriene46; consequently, use during pregnancy is not recommended.1,46 Some authors recommend against topical salicylic acid in pregnancy; others report that limited exposure is permissible.47 In fact, as salicylic acid commonly is found in over-the-counter acne products, many women of childbearing potential likely have quotidian exposure.

Preterm delivery and low birthweight have been reported with oral tacrolimus; however, risk with topical tacrolimus is thought to be low1 because the molecular size likely prohibits notable absorption.47 Evidence for the use of anthralin and coal tar also is scarce. First-trimester coal tar use should be avoided; subsequent use in pregnancy should be restricted given concern for adverse outcomes.1

 

 



Phototherapy
Broadband or narrowband UVB therapy is recommended as second-line therapy in pregnancy. No cases of fetal risk or premature delivery associated with UVB therapy were found in our search.1 Phototherapy can exacerbate melasma47 and decrease folate levels48; as such, some authors recommend folate supplementation in females of childbearing age who are being treated with phototherapy.49 Psoralen, used in psoralen plus UVA therapy, is mutagenic and therefore contraindicated in pregnancy.1

Oral Medications
Both methotrexate, which is a teratogen, abortifacient, and mutagen,1 and systemic retinoids, which are teratogens, are contraindicated in pregnancy.1,47 Acitretin labeling recommends avoiding pregnancy for 3 years posttreatment50 because alcohol intake prolongs the medication’s half-life.22



Apremilast use is not documented in pregnant psoriasis patients51; an ongoing registry of the Organization of Tetralogy Information Specialists has not reported publicly to date.52 Animal studies of apremilast have documented dose-related decreased birthweight and fetal loss.22

Safety data for systemic steroids, used infrequently in psoriasis, are not well established. First-trimester prednisone exposure has been associated with prematurity, low birthweight, and congenital abnormalities.38 A separate evaluation of 1047 children exposed to betamethasone in utero failed to demonstrate significant change in birthweight or head circumference. However, repeat antenatal corticosteroid exposure was associated with attention problems at 2 years of age.39

Data regarding cyclosporine use, derived primarily from organ transplant recipients, suggest elevated risk for prematurity and low birthweight.53,54 A meta-analysis demonstrated that organ transplant recipients taking cyclosporine had a nonsignificantly elevated odds ratio for congenital malformations, prematurity, and low birthweight.42 Cyclosporine use for psoriasis in pregnancy is not well described; in a study, rates of prematurity and low birthweight were both 21%.43 Limited data are available for Janus kinase inhibitors, none of which are approved for psoriasis, though clinical trials in psoriasis and psoriatic arthritis are underway (ClinicalTrials.gov identifiers NCT04246372, NCT03104374, NCT03104400).

Biologics and Small-Molecule Inhibitors
Limited data on biologics in pregnancy exist25 (eTable 3). Placental transport of IgG antibodies, including biologics, increases throughout pregnancy, especially in the third trimester.82 Infants of mothers treated with a biologic with potential for placental transfer are therefore considered by some authors to be immunosuppressed during the first months of life.2

Looking globally across biologics used for psoriasis, limited safety data are encouraging. In a review of PSOLAR (Psoriasis Longitudinal Assessment and Registry), 83 pregnancies with biologic exposure resulted in 59 live births (71%); 18 spontaneous abortions (22%); 6 induced abortions (7%); no congenital abnormalities; and 7 reports of neonatal problems, including respiratory issues, ABO blood group mismatch, hospitalization, and opioid withdrawal.83

Use of tumor necrosis factor (TNF) inhibitors in pregnancy has the most data25 and is considered a reasonable treatment option. Historically, there was concern about the risk for VACTERL syndrome (vertebral defects, anal atresia, cardiac defects, tracheoesophageal fistula, renal anomalies, limb abnormalities) with exposure to a TNF inhibitor,25,84-86 but further reports have alleviated these concerns. Active transplacental transport occurs for adalimumab, infliximab, and golimumab,87 but given structural differences, transport of certolizumab and etanercept is substantially less.88,89 In the CRIB study of placental transfer of certolizumab from mother to infant (N=14), pharmacokinetic data demonstrated no quantifiable certolizumab levels in 13 infants and minimal levels in 1 infant at birth.88 There are fewer data available on the use of other biologics in pregnancy, but for those in which active placental transport is relevant, similar concerns (ie, immunosuppression) might arise (eTable 3).

Concern over biologics largely involves risk for newborn immunosuppression. A case report detailed a Crohn disease patient treated with infliximab who gave birth to an infant who died of disseminated bacille Calmette-Guérin infection at 4.5 months after receiving the vaccine at 3 months.90 This case underscores the importance of delaying live vaccination in infants born to mothers who were treated with a biologic during pregnancy. Authors have provided various data on how long to avoid vaccination; some state as long as 1 year.91

In pregnant females with inflammatory bowel disease treated with a biologic, no correlation was observed among maternal, placental, and infant serum biologic levels and neonatal infection. However, an association between preterm birth and the level of the biologic in maternal and placental (but not infant) serum and preterm birth was observed.92



In another report from the same registry, combination therapy with a TNF inhibitor and another immunomodulator led to an increased risk for infection in infants at 12 months of age, compared to infants exposed to monotherapy89 or exposed to neither agent.93 A strategy to circumvent this potential problem is to avoid treatment with actively transported molecules in the third trimester.

Conclusion

Limited data exist to guide providers who are treating pregnant women with psoriasis. Our understanding of treatment of psoriasis in pregnancy is limited as a consequence of regulations surrounding clinical trials and inadequate detection of pregnancies in registries. Further efforts are necessary to better understand the relationship between psoriasis and pregnancy and how to manage pregnant women with psoriasis.

References
  1. Bae YS, Van Voorhees AS, Hsu S, et al. Review of treatment options for psoriasis in pregnant or lactating women: from the medical board of the National Psoriasis Foundation. J Am Acad Dermatol. 2012;67:459-477.
  2. Menter A, Strober BE, Kaplan DH, et al. Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with biologics. J Am Acad Dermatol. 2019;80:1029-1072.
  3. Flood KS, Porter ML, Kimball AB. Use of biologics in pregnancy: limitations stemming from clinical trials and registry experience. J Eur Acad Dermatol Venereol. 2019;33:E276-E277.
  4. Horn EJ, Chambers CD, Menter A, et al. Pregnancy outcomes in psoriasis: why do we know so little? J Am Acad Dermatol. 2009;61:E5-E8.
  5. Raychaudhuri SP, Navare T, Gross J, et al. Clinical course of psoriasis during pregnancy. Int J Dermatol. 2003;42:518-520.
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  7. Murase JE, Chan KK, Garite TJ, et al. Hormonal effect on psoriasis in pregnancy and post partum. Arch Dermatol. 2005;14:601-606.
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  27. Lima XT, Janakiraman V, Hughes MD, et al. The impact of psoriasis on pregnancy outcomes. J Invest Dermatol. 2012;132:85-91.
  28. Bröms G, Haerskjold A, Granath F, et al. Effect of maternal psoriasis on pregnancy and birth outcomes: a population-based cohort study from Denmark and Sweden. Acta Derm Venereol. 2018;98:728-734.
  29. Bobotsis R, Gulliver WP, Monaghan K, et al. Psoriasis and adverse pregnancy outcomes: a systematic review of observational studies. Br J Dermatol. 2016;175:464-472.
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  33. Chi CC, Wang SH, Kirtschig G. Safety of topical corticosteroids in pregnancy. JAMA Dermatol. 2016;152:934-935.
  34. Dovonex (calcipotriene) Cream, 0.005% [package insert]. Dublin, Ireland: Leo Laboratories, Ltd; March 2015.
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  36. Garbis H, Elefant E, Bertolotti E, et al. Pregnancy outcome after periconceptional and first-trimester exposure to methoxsalen photochemotherapy. Arch Dermatol. 1995;131:492-493.
  37. Horizon Pharma USA. RAYOS (prednisone). https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/202020s000lbl.pdf https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/202020s000lbl.pdf.
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  39. Crowther CA, Doyle LW, Haslam RR, et al. Outcomes at 2 years of age after repeat doses of antenatal corticosteroids. N Engl J Med. 2007;357:1179-1189.
  40. Palmsten K, Rolland M, Herbert MF, et al. Patterns of prednisone use during pregnancy in women with rheumatoid arthritis: daily and cumulative dose. Pharmacoepidemiol Drug Saf. 2018;27:430-438.
  41. Groth K, Brännström M, Mölne J, et al. Cyclosporine A exposure during pregnancy in mice: effects on reproductive performance in mothers and offspring. Hum Reprod. 2010;25:697-704.
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  43. Paziana K, Del Monaco M, Cardonick E, et al. Ciclosporin use during pregnancy. Drug Saf. 2013;36:279-294.
  44. Lamarque V, Leleu MF, Monka C, et al. Analysis of 629 pregnancy outcomes in transplant recipients treated with Sandimmun. Transplant Proc. 1997;29:2480.
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  46. Kurizky PS, de Castro Ferreira C, Nogueira LSC, et al. Treatment of psoriasis and psoriatic arthritis during pregnancy and breastfeeding. An Bras Dermatol. 2015;90:367-375.
  47. Murase JE, Heller MM, Butler DC. Safety of dermatologic medications in pregnancy and lactation. J Am Acad Dermatol. 2014;70:401.e1-401.e4.
  48. El-Saie LT, Rabie AR, Kamel MI, et al. Effect of narrowband ultraviolet B phototherapy on serum folic acid levels in patients with psoriasis. Lasers Med Sci. 2011;26:481-485.
  49. Murase JE, Koo JY, Berger TG. Narrowband ultraviolet B phototherapy influences serum folate levels in patients with vitiligo. J Am Acad Dermatol. 2010;62:710-711.
  50. Soriatane (acitretin) capsules [package insert]. Morrisville, NC: Stiefel Laboratories, Inc; April 2011. http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/019821s018mg.pdf. Accessed July 8, 2020.
  51. Kaushik SB, Lebwohl MG. Psoriasis: which therapy for which patient: focus on special populations and chronic infections. J Am Acad Dermatol. 2019;80:43-53.
  52. Help us better understand the effects of Otezla in pregnancy. MotherToBaby website. https://mothertobaby.org/ongoing-study/otezla/. Accessed July 8, 2020.
  53. Bangsgaard N, Rørbye C, Skov L. Treating psoriasis during pregnancy: safety and efficacy of treatments. Am J Clin Dermatol. 2015;16:389-398.
  54. Tyler K. Dermatologic therapy in pregnancy. Clin Obstet Gynecol. 2015;58:112-118.
  55. Luu M, Benzenine E, Doret M, et al. Continuous anti–TNF-α use throughout pregnancy: possible complications for the mother but not for the fetus. a retrospective cohort on the French National Health Insurance Database (EVASION). Am J Gastroenterol. 2018;113:1669-1677.
  56. Bröms G, Granath F, Ekbom A, et al. Low risk of birth defects for infants whose mothers are treated with anti-tumor necrosis factor agents during pregnancy. Clin Gastroenterol Hepatol. 2016;14:234-241.
  57. Mirdamadi K, Salinas T, Vali R, et al. Meta-analysis of pregnancy outcomes after exposure to TNF-α inhibitors during pregnancy for the treatment of arthritic diseases. J Popul Ther Clin Pharmacol. 2018;25:E53-E56.
  58. Shihab Z, Yeomans ND, De Cruz P. Anti-tumour necrosis factor α therapies and inflammatory bowel disease pregnancy outcomes: a meta-analysis. J Crohns Colitis. 2016;10:979-988.
  59. Bröms G, Kieler H, Ekbom A, et al. Anti-TNF treatment during pregnancy and birth outcomes: a population-based study from Denmark, Finland, and Sweden. Pharmacoepidemiol Drug Saf. 2020;29:316-327.
  60. Diav-Citrin O, Otcheretianski-Volodarsky A, Shechtman S, et al. Pregnancy outcome following gestational exposure to TNF-alpha-inhibitors: a prospective, comparative, observational study. Reprod Toxicol. 2014;43:78-84.
  61. FDA determinations for pregnant and nursing women. National Psoriasis Foundation website. http://www.psoriasis.org/pregnancy/fda-determinations. Accessed July 8, 2020.
  62. Østensen M. Safety issues of biologics in pregnant patients with rheumatic diseases. Ann N Y Acad Sci. 2014;1317:32-38.
  63. Chambers CD, Johnson DL, Luo Y, et al. Pregnancy outcome in women treated with adalimumab for the treatment of rheumatoid arthritis: the OTIS Autoimmune Diseases in Pregnancy Project. Arthritis Rheum. 2012;64:2466.
  64. Clowse ME, Wolf DC, Forger F, et al. Pregnancy outcomes after exposure to certolizumab pegol: updated results from a pharmacovigilance safety database. Arthritis Rheumatol. 2018;70:1399-1407.
  65. Carman WJ, Accortt NA, Anthony MS, et al. Pregnancy and infant outcomes including major congenital malformations among women with chronic inflammatory arthritis or psoriasis, with and without etanercept use. Pharmacoepidemiol Drug Saf. 2017;26:1109-1118.
  66. Janssen. SIMPONI (golilumab). https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/125289s0064lbl.pdf.
  67. Yurkon K, Guo CY, Harrison D, et al. Pregnancy outcomes in women with dermatologic conditions exposed to infliximab. J Am Acad Dermatol. 2014;70:AB179.
  68. Watson N, Wu K, Farr P, et al. Ustekinumab exposure during conception and pregnancy in patients with chronic plaque psoriasis: a case series of 10 pregnancies. Br J Dermatol. 2019;180:195-196.
  69. Naureckas S, Slater J, Gearhart N, et al. Pregnancy outcomes in women with psoriasis and psoriatic arthritis exposed to ustekinumab. J Am Acad Dermatol. 2016;74:AB264.
  70. Haycraft K, DiRuggiero D, Rozzo SJ, et al. Outcomes of pregnancies from tildrakizumab phases I to III clinical development program. J Clin Aesthet Dermatol. 2019;12:S27-S28.
  71. Tremfya (guselkumab) injection, for subcutaneous use [package insert]. Horsham, PA: Janssen Biotech, Inc; July 2017. http://www.accessdata.fda.gov/drugsatfda_docs/label/2017/761061s000lbl.pdf. Accessed Juy 8, 2020.
  72. Skyrizi (risankizumab-rzaa) injection, for subcutaneous use [package insert]. Northi Chicago, IL; April 2019. http://www.accessdata.fda.gov/drugsatfda_docs/label/2019/761105s000lbl.pdf. Accessed July 8, 2020.
  73. Siliq (brodalumab) injection, for subcutaneous use [package insert]. Bridgewater, NJ: Valeant Pharmaceuticals North America LLC; February 2017. http://www.accessdata.fda.gov/drugsatfda_docs/label/2017/761032lbl.pdf. Accessed July 8, 2020.
  74. Feldman S, Pangallo B, Xu W, et al. Ixekizumab and pregnancy outcome. J Am Acad Dermatol. 2017;76:AB419.
  75. Clarke DO, Hilbish KG, Waters DG, et al. Assessment of ixekizumab, an interleukin-17A monoclonal antibody, for potential effects on reproduction and development, including immune system function, in cynomolgus monkeys. Reprod Toxicol. 2015;58:160-173.
  76. Warren RB, Reich K, Langley RG, et al. Secukinumab in pregnancy: outcomes in psoriasis, psoriatic arthritis and ankylosing spondylitis from the global safety database. Br J Dermatol. 2018;179:1205-1207.
  77. Nardin C, Colas M, Curie V, et al. Pregnancy after tubal sterilization in a woman treated with biologics for severe psoriasis. Dermatol Ther (Heidelb). 2018;8:323-326.
  78. Xeljanz (tofacitinib) tablets for oral administration [package insert]. New York, NY: Pfizer; November 2012. http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203214s000lbl.pdf. Accessed July 8, 2020.
  79. Pfizer. Xeljanz (tofacitinib). https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/203214s018lbl.pdf.
  80. Mahadevan U, Dubinsky M, Su C, et al. Outcomes of pregnancies with maternal/paternal exposure in the tofacitinib safety databases for ulcerative colitis. Inflamm Bowel Dis. 2018;24:2494-2500.
  81. Clowse ME, Feldman SR, Isaacs JD, et al. Pregnancy outcomes in the tofacitinib safety databases for rheumatoid arthritis and psoriasis. Drug Saf. 2016;39:755-762.
  82. Malek A, Sager R, Kuhn P, et al. Evolution of maternofetal transport of immunoglobulins during human pregnancy. Am J Reprod Immunol. 1996;36:248-255.
  83. Kimball AB, Crow JA, Ridley K, et al. Pregnancy outcomes in women with moderate to severe psoriasis: the PSOLAR experience. J Am Acad Dermatol. 2014;70(suppl 1):AB179.
  84. Carter JD, Valeriano J, Vasey FB. Tumor necrosis factor-alpha inhibition and VATER association: a causal relationship. J Rheumatol. 2006;33:1014-1017.
  85. Carter JD, Ladhani A, Ricca LR, et al. A safety assessment of tumor necrosis factor antagonists during pregnancy: a review of the Food and Drug Administration database. J Rheumatol. 2009;36:635-641.
  86. Koren G, Inoue M. Do tumor necrosis factor inhibitors cause malformations in humans? J Rheumatol. 2009;36:465-466.
  87. Johansen C, Jimenez-Solem E, Haerskjold A, et al. The use and safety of TNF inhibitors during pregnancy in women with psoriasis: a review. Int J Mol Sci. 2018;19:E1349.
  88. Mariette X, Forger F, Abraham B, et al. Lack of placental transfer of certolizumab pegol during pregnancy: results from CRIB, a prospective, postmarketing, pharmacokinetic study. Ann Rheum Dis. 2018;77:228-233.
  89. Mahadevan U, Wolf DC, Dubinsky M, et al. Placental transfer of anti-tumor necrosis factor agents in pregnant patients with inflammatory bowel disease. Clin Gastroenterol Hepatol. 2013;11:286-292.
  90. Cheent K, Nolan J, Sharig S, et al. Case report: fatal case of disseminated BCG infection in an infant born to a mother taking infliximab for Crohn’s disease. J Crohns Colitis. 2010;4:603-605.
  91. Julsgaard M, Christensen LA, Gibson PR, et al. Concentrations of adalimumab and infliximab in mothers and newborns, and effects on infection. Gastroenterology. 2016;151:110-119.
  92. Mahadevan U, Martin C, Kane SV, et al. Do infant serum levels of biologic agents at birth correlate with risk of adverse outcomes? results from the PIANO registry. Gastroenterology. 2016;150:S91-S92.
  93. Mahadevan U, Martin CF, Sandler RS, et al. PIANO: a 1000 patient prospective registry of pregnancy outcomes in women with IBD exposed to immunomodulators and biologic therapy [AGA abstract 865]. Gastroenterology. 2012;142:S-149.
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  56. Bröms G, Granath F, Ekbom A, et al. Low risk of birth defects for infants whose mothers are treated with anti-tumor necrosis factor agents during pregnancy. Clin Gastroenterol Hepatol. 2016;14:234-241.
  57. Mirdamadi K, Salinas T, Vali R, et al. Meta-analysis of pregnancy outcomes after exposure to TNF-α inhibitors during pregnancy for the treatment of arthritic diseases. J Popul Ther Clin Pharmacol. 2018;25:E53-E56.
  58. Shihab Z, Yeomans ND, De Cruz P. Anti-tumour necrosis factor α therapies and inflammatory bowel disease pregnancy outcomes: a meta-analysis. J Crohns Colitis. 2016;10:979-988.
  59. Bröms G, Kieler H, Ekbom A, et al. Anti-TNF treatment during pregnancy and birth outcomes: a population-based study from Denmark, Finland, and Sweden. Pharmacoepidemiol Drug Saf. 2020;29:316-327.
  60. Diav-Citrin O, Otcheretianski-Volodarsky A, Shechtman S, et al. Pregnancy outcome following gestational exposure to TNF-alpha-inhibitors: a prospective, comparative, observational study. Reprod Toxicol. 2014;43:78-84.
  61. FDA determinations for pregnant and nursing women. National Psoriasis Foundation website. http://www.psoriasis.org/pregnancy/fda-determinations. Accessed July 8, 2020.
  62. Østensen M. Safety issues of biologics in pregnant patients with rheumatic diseases. Ann N Y Acad Sci. 2014;1317:32-38.
  63. Chambers CD, Johnson DL, Luo Y, et al. Pregnancy outcome in women treated with adalimumab for the treatment of rheumatoid arthritis: the OTIS Autoimmune Diseases in Pregnancy Project. Arthritis Rheum. 2012;64:2466.
  64. Clowse ME, Wolf DC, Forger F, et al. Pregnancy outcomes after exposure to certolizumab pegol: updated results from a pharmacovigilance safety database. Arthritis Rheumatol. 2018;70:1399-1407.
  65. Carman WJ, Accortt NA, Anthony MS, et al. Pregnancy and infant outcomes including major congenital malformations among women with chronic inflammatory arthritis or psoriasis, with and without etanercept use. Pharmacoepidemiol Drug Saf. 2017;26:1109-1118.
  66. Janssen. SIMPONI (golilumab). https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/125289s0064lbl.pdf.
  67. Yurkon K, Guo CY, Harrison D, et al. Pregnancy outcomes in women with dermatologic conditions exposed to infliximab. J Am Acad Dermatol. 2014;70:AB179.
  68. Watson N, Wu K, Farr P, et al. Ustekinumab exposure during conception and pregnancy in patients with chronic plaque psoriasis: a case series of 10 pregnancies. Br J Dermatol. 2019;180:195-196.
  69. Naureckas S, Slater J, Gearhart N, et al. Pregnancy outcomes in women with psoriasis and psoriatic arthritis exposed to ustekinumab. J Am Acad Dermatol. 2016;74:AB264.
  70. Haycraft K, DiRuggiero D, Rozzo SJ, et al. Outcomes of pregnancies from tildrakizumab phases I to III clinical development program. J Clin Aesthet Dermatol. 2019;12:S27-S28.
  71. Tremfya (guselkumab) injection, for subcutaneous use [package insert]. Horsham, PA: Janssen Biotech, Inc; July 2017. http://www.accessdata.fda.gov/drugsatfda_docs/label/2017/761061s000lbl.pdf. Accessed Juy 8, 2020.
  72. Skyrizi (risankizumab-rzaa) injection, for subcutaneous use [package insert]. Northi Chicago, IL; April 2019. http://www.accessdata.fda.gov/drugsatfda_docs/label/2019/761105s000lbl.pdf. Accessed July 8, 2020.
  73. Siliq (brodalumab) injection, for subcutaneous use [package insert]. Bridgewater, NJ: Valeant Pharmaceuticals North America LLC; February 2017. http://www.accessdata.fda.gov/drugsatfda_docs/label/2017/761032lbl.pdf. Accessed July 8, 2020.
  74. Feldman S, Pangallo B, Xu W, et al. Ixekizumab and pregnancy outcome. J Am Acad Dermatol. 2017;76:AB419.
  75. Clarke DO, Hilbish KG, Waters DG, et al. Assessment of ixekizumab, an interleukin-17A monoclonal antibody, for potential effects on reproduction and development, including immune system function, in cynomolgus monkeys. Reprod Toxicol. 2015;58:160-173.
  76. Warren RB, Reich K, Langley RG, et al. Secukinumab in pregnancy: outcomes in psoriasis, psoriatic arthritis and ankylosing spondylitis from the global safety database. Br J Dermatol. 2018;179:1205-1207.
  77. Nardin C, Colas M, Curie V, et al. Pregnancy after tubal sterilization in a woman treated with biologics for severe psoriasis. Dermatol Ther (Heidelb). 2018;8:323-326.
  78. Xeljanz (tofacitinib) tablets for oral administration [package insert]. New York, NY: Pfizer; November 2012. http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203214s000lbl.pdf. Accessed July 8, 2020.
  79. Pfizer. Xeljanz (tofacitinib). https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/203214s018lbl.pdf.
  80. Mahadevan U, Dubinsky M, Su C, et al. Outcomes of pregnancies with maternal/paternal exposure in the tofacitinib safety databases for ulcerative colitis. Inflamm Bowel Dis. 2018;24:2494-2500.
  81. Clowse ME, Feldman SR, Isaacs JD, et al. Pregnancy outcomes in the tofacitinib safety databases for rheumatoid arthritis and psoriasis. Drug Saf. 2016;39:755-762.
  82. Malek A, Sager R, Kuhn P, et al. Evolution of maternofetal transport of immunoglobulins during human pregnancy. Am J Reprod Immunol. 1996;36:248-255.
  83. Kimball AB, Crow JA, Ridley K, et al. Pregnancy outcomes in women with moderate to severe psoriasis: the PSOLAR experience. J Am Acad Dermatol. 2014;70(suppl 1):AB179.
  84. Carter JD, Valeriano J, Vasey FB. Tumor necrosis factor-alpha inhibition and VATER association: a causal relationship. J Rheumatol. 2006;33:1014-1017.
  85. Carter JD, Ladhani A, Ricca LR, et al. A safety assessment of tumor necrosis factor antagonists during pregnancy: a review of the Food and Drug Administration database. J Rheumatol. 2009;36:635-641.
  86. Koren G, Inoue M. Do tumor necrosis factor inhibitors cause malformations in humans? J Rheumatol. 2009;36:465-466.
  87. Johansen C, Jimenez-Solem E, Haerskjold A, et al. The use and safety of TNF inhibitors during pregnancy in women with psoriasis: a review. Int J Mol Sci. 2018;19:E1349.
  88. Mariette X, Forger F, Abraham B, et al. Lack of placental transfer of certolizumab pegol during pregnancy: results from CRIB, a prospective, postmarketing, pharmacokinetic study. Ann Rheum Dis. 2018;77:228-233.
  89. Mahadevan U, Wolf DC, Dubinsky M, et al. Placental transfer of anti-tumor necrosis factor agents in pregnant patients with inflammatory bowel disease. Clin Gastroenterol Hepatol. 2013;11:286-292.
  90. Cheent K, Nolan J, Sharig S, et al. Case report: fatal case of disseminated BCG infection in an infant born to a mother taking infliximab for Crohn’s disease. J Crohns Colitis. 2010;4:603-605.
  91. Julsgaard M, Christensen LA, Gibson PR, et al. Concentrations of adalimumab and infliximab in mothers and newborns, and effects on infection. Gastroenterology. 2016;151:110-119.
  92. Mahadevan U, Martin C, Kane SV, et al. Do infant serum levels of biologic agents at birth correlate with risk of adverse outcomes? results from the PIANO registry. Gastroenterology. 2016;150:S91-S92.
  93. Mahadevan U, Martin CF, Sandler RS, et al. PIANO: a 1000 patient prospective registry of pregnancy outcomes in women with IBD exposed to immunomodulators and biologic therapy [AGA abstract 865]. Gastroenterology. 2012;142:S-149.
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  • Robust safety data often are lacking for the use of topical and systemic agents to treat psoriasis in pregnancy.
  • Professional society guidelines on the use of systemic agents in pregnancy vary among dermatology, gastroenterology, and rheumatology organizations.
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