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Dear Editor, Psoriasis, psoriatic arthritis (PsA) and ankylosing spondylitis (AS) are chronic inflammatory conditions. Effective long‐term treatment may be necessary in women of childbearing age, but data concerning current treatments and pregnancy remain incomplete. Due to immunological changes, psoriasis and, to a lesser extent, PsA generally improve during pregnancy;1,2 however, many pregnant patients still require treatment. AS tends to have an adverse effect on health‐related quality of life during pregnancy.3 There is growing evidence to suggest that biological treatments for inflammatory conditions are not detrimental during pregnancy.1 Secukinumab is a fully human monoclonal antibody that selectively targets ilnterleukin‐17A, and shows sustained efficacy in the treatment of moderate‐to‐severe psoriasis, PsA and AS, with a favourable safety profile.4,5 As an IgG1 molecule, secukinumab could theoretically cross the placenta, but most antibody transfer occurs in the third trimester.6 Animal studies do not indicate harmful effects of secukinumab with respect to pregnancy, embryonic or fetal development, parturition or postnatal development, including the immune morphology and response (Novartis data on file; spermatogenesis not studied). The effect of secukinumab on pregnancy outcomes or spermatogenesis has not been studied in clinical trials; all studies in the secukinumab clinical trials programme excluded pregnant women, and study medication had to be discontinued if a patient became pregnant. The prescribing information for secukinumab states that, as a precautionary measure, it is preferable to avoid use in pregnancy. Using the Novartis global safety database, the outcomes of pregnancies where there was maternal or paternal exposure to secukinumab were analysed. The Novartis global safety database covers any adverse events reported in all secukinumab indications and includes 11 140 clinical trial patients and 96 054 patient‐years of postmarketing data. The database was searched for cases reporting pregnancy and neonatal topics, using MedDRA version 19·1 with the standard MedDRA query (broad) ‘pregnancy and neonatal topics’. All pregnancies where there was either maternal or paternal exposure to secukinumab were included in the systematic, independently validated analysis. Data were collected using standard follow‐up procedures including repeated attempts at pre‐ and postnatal follow‐up. The cut‐off date was 25 June 2017. There were 292 pregnancies reported in the safety database. Overall, 141 (48·3%) came from clinical trials, 79 (27·1%) were spontaneous reports and 72 (24·7%) were from postmarketing surveillance, with 238 cases of maternal and 54 of paternal exposure (Table 1). The secukinumab dose was 300 mg in 125 patients (42·8%), 150 mg in 19 (6·5%) and unknown in 148 (50·7%). Pregnancy outcomes from the secukinumab global safety database Values are n (%) except for age. aMean mother's age for 164 patients, age of 74 patients was unknown. bMean father's age for 28 patients, age of 26 patients was unknown. cCongenital malformations included ventricular septal defect with minor left–right shunt (n = 1), Angelman syndrome (deleted 15q11·2q13·1; n = 1), and club foot, right hand underdeveloped and short fingers (n = 1). dUp to 20 weeks of gestation. Pregnancy outcomes from the secukinumab global safety database Values are n (%) except for age. aMean mother's age for 164 patients, age of 74 patients was unknown. bMean father's age for 28 patients, age of 26 patients was unknown. cCongenital malformations included ventricular septal defect with minor left–right shunt (n = 1), Angelman syndrome (deleted 15q11·2q13·1; n = 1), and club foot, right hand underdeveloped and short fingers (n = 1). dUp to 20 weeks of gestation. A greater number of pregnancy outcomes were known for clinical trials (113 of 142, 79·6%) than for cases reported during postmarketing surveillance (41 of 150, 27·3%). Of the cases where the outcome was known, there were 73 full‐term healthy neonates (Table 1). Rates of spontaneous abortions overall (30 of 292, 10·3%) were in line with observed rates for the general population with the mean maternal age of 30·6 years (15–20%).7 Rates of spontaneous abortion for patients with known outcomes were 30 of 153 (19·6%), again in accordance with established rates. Most spontaneous abortions occurred within 10 weeks of pregnancy and there were no stillbirths (> 20 weeks’ gestation). The majority of patients (where known) discontinued secukinumab in the first trimester of pregnancy (155, 65·1%; Table 1). There were 18 maternal cases who did not discontinue treatment, three of whom continued treatment throughout pregnancy or discontinued in the third trimester. Within these 18 cases there were four elective terminations, three spontaneous abortions, one pregnancy ongoing, one healthy neonate and nine cases lost to follow‐up or unknown. Three congenital abnormalities were reported (three of 292, 1·0% overall; three of 153, 2·0% in patients with known outcomes), in line with the general population rate (2·4%),8 and there was no pattern of abnormality (Table 1). Secukinumab was not suspected to be linked to any of these cases by the treating physician. Although patient numbers were small and follow‐up was limited, no clear differences in outcomes were observed between the different indications. Of 38 cases of exposure in patients with PsA, spontaneous abortions occurred in 8%. In 15 patients with AS the rate was 7%. This cohort of pregnant patients taking secukinumab for psoriasis, PsA and AS adds to existing evidence for the safety of biologics in pregnancy.1 No safety signals were identified regarding spontaneous abortions or congenital malformations. In clinical practice, these data provide reassurance in cases where conception occurs during secukinumab treatment. However, this analysis is limited by the large amount of missing outcome data and the relatively short exposure to secukinumab. The majority of patients discontinued in the first trimester, whereas secukinumab would be expected to be transferred across the placenta in the third trimester. There are no human data on the effects of secukinumab on the immune system of neonates born after in utero exposure. Although there may be a bias towards reporting of detrimental events, there was no evidence for increased rates of adverse pregnancy outcomes with secukinumab in this review of the safety database. However, given the limited exposure reported to date, the continuous use of secukinumab throughout pregnancy requires further research. Funding sources: Novartis Pharma AG. Conflicts of interest: See supporting information
Warren et al. (Thu,) studied this question.