Use of biologic agents for rheumatic diseases in pregnancy

Table 1 An overview of published data from case reports, case series and registries on biologic agents

Ref.	Study design	No. of pregnancies	Diagnosis	Biologic agent	Time of exposure	Reported outcomes
Bortlik et al[16]	Case series	41	27 CD 14 UK	INF ETA	NR	5 spontaneous abortion 2 elective termination 1 congenital malformation (mild hip dysplasia)
Burt et al[19]	Case report	1	CD	INF	T1	Healthy infant at 36 wk of gestation
Sinha and Patient[20]	Case report	1	RA	ETA	C + T1 + T2 + T3	Healthy term delivery
Takayama et al[21]	Case report	1	BD	INF	T2 + T3 (discontinued at 32 wk of gestation)	Healthy term delivery
Coburn et al[22]	Case report	1	CD	ADA	T2 + T3	Healthy term delivery
Akinci et al[23]	Case report	1	AS	INF	T2 + T3	Healthy term delivery
Kraemer et al[24]	Case report	1	Takayasu arteritis	ADA	C + T1 + T2 + T3	Healthy term delivery
Hou et al[25]	Case report	1	CD	INF	T1 + T2 + T3 (discontinued at 33 wk of gestation)	Healthy term delivery
Umeda et al[26]	Case report	1	RA	ETA	T2 + T3	Healthy term delivery
Puig et al[27]	Case report	1	Psoriasis	INF	T1 + T2 + T3 (last infusion at 29 wk of gestation)	Healthy term delivery
Jang et al[28]	Case report	1	CD	INF	C + T1	Healthy term delivery
Vesga et al[29]	Case report	1	CD	ADA	C + T1 + T2 + T3	Healthy term delivery
Mahadevan et al[30]	Case series	10	CD	INF	NR	10 live birth 3 premature delivery 0 spontaneous abortion 0 elective termination 0 congenital malformation
Berthelot et al[31]	Case series	15	SpA, RA, JIA, PsA	3 INF 2 ADA 10 ETA	NR	2 spontaneous abortion (ETA) 1 elective termination (ETA)
Rump et al[33]	Case series	8 pregnancies in 5 women	4 RA 1 AS	ETA	NR	1 spontaneous abortion 1 megacolon congenitum
Arguelles-Arias et al[34]	Case series	12	8 CD 4 UK	INF	1 C 2 T1 3 T1 + T2 6 T1 + T2 + T3	1 premature delivery No congenital malformation, IUGR, SGA
Diav-Citrin et al[35]	Registry	83	CD, RA, UK, UndA, PsA, AS, BD	35 INF 25 ETA 23 ADA	81 T1 2 T2 or T3	67 live birth 9 spontaneous abortion 5 elective termination 0 congenital malformation
Chakravarty et al[36]	Registry	17	RA	15 ETA 2 INF	NR	1 spontaneous abortion (ETA) 1 elective termination (ETA) No congenital malformation, IUGR, SGA
Hyrich et al[37]	Registry	23	RA	17 ETA 3 INF 3 ADA	NR	14 live births 6 spontaneous abortion (4 ETA, 1 INF, 1 ADA) 3 elective termination (all in patients receiving ETA, 2 also receiving MTX)
Carter et al[38]	Registry	41	Autoimmune diseases	22 ETA 19 INF	NR	24 (59%) children had one or more congenital deformities such as vertebral deformities, anal atresia, cardiac anomalies, tracheoesophageal fistula, renal anomalies and limb defects, which were the features of VACTERL
Offiah et al[40]	Case report	1	PsA	INF	C + T1 + T2 + T3	Transient collodion membrane
Guiddir et al[41]	Case series	4	UK	INF	T1 + T2 + T3	4 neonatal neutropenia
Grosen et al[44]	Case report	1	UK	INF	T3	Ten days after INF infusion serum sickness-like reaction in the mother (at 35 wk of gestation) Preterm infant without any congenital anomaly
Ergaz et al[45]	Case report	1	RA	ETA (also receiving prednisone and hydroxychloroquine	C + T1 + T2 + T3	Congenital fulminant kaposiform hemangioendothelioma
Hultzsch et al[46]	Case series	26	19 RA 6 AS 1 PsA	ETA	T1	19 live birth 5 premature delivery 5 spontaneous abortion 2 elective termination 1 congenital renal agenesis 1 hypoplastic left heart syndrome + hypospadias 1 Wolff Parkinson White syndrome
Weber-Schoendorfer et al[47]	Case series	53	Autoimmune diseases	28 ADA 25 INF	T1	46 live birth (24 ADA, 22 INF) 8 premature delivery (4 ADA, 4 INF) 4 spontaneous abortion (2 ADA, 2 INF) 3 elective termination (2 ADA, 1 INF) 1 autosomal disease inherited from his father (ADA) 1 ventricular septal defect (INF)
Johnson et al[48]	Case series	34	RA	ADA	T1	29 live birth 5 spontaneous abortion 1 undescended testicle 1 microcephaly
Katz et al[49]	Registry	64	82 CD 8 RA 2 JRA 1 UK	INF	53 within 3 mo of C 25 within 3 mo prior to C 28 within 3 mo prior to C + T1 30 T1 7 > 3 mo prior to C 6 unknown	64 live birth 14 spontaneous abortion 18 therapeutic termination 0 congenital malformation
Cheent et al[50]	Case report	1	CD	INF	C + T1 + T2 + T3	No congenital malformation, IUGR BCG vaccination at age of 3 mo Died from disseminated BCG disease at age of 4.5 mo
Mahadevan et al[51]	Registry	190	124 CD 56 other diseases	CZP	NR	132 live birth 36 spontaneous abortion 22 elective termination vesicoureteral reflux, congenital morbus, congenital megacolon, congenital talipes equinovarus, aortic arch anomaly, and unilateral hydronephrosis in four infants
Lau et al[56]	Case series	40	24 RA 1 PsA 5 AS 10 UK	GLM	NR	19 live birth 13 spontaneous abortion 7 induced abortion 1 ectopic pregnancy 1 unspecific congenital malformation leading to intrauterine death and induced abortion
Berger et al[57]	Case report	1	AOSD	Anakinra	C + T1 + T2 + T3	Term delivery complicated with placental retention
Chang et al[59]	Case series	9	CAPS	Anakinra	C + T1 + T2 + T3	No preterm birth or serious complication Fetal loss of a twin due to renal agenesis. DNA testing revealed the same NLRP3 c.785T > C, p.V262A mutation as the mother
Rubbert-Roth et al[60]	Registry	33	RA	TCZ	NR	7 spontaneous abortion 13 elective termination 11 term delivery (1 infant died from ARDS 3 d after emergency cesarean section for intrapartum fetomaternal hemorrhage due to placenta previa)
Ojeda-Uribe et al[61]	Case series	3	Autoimmune diseases	2 RTX 1 abatacept	T1	3 healthy term delivery
Chakravarty et al[64]	Registry	153	Autoimmune diseases	RTX	NR	90 live birth 33 spontaneous abortion 28 elective termination 22 premature delivery 1 maternal death from autoimmune thrombocytopenia 1 perinatal death 11 perinatal hematologic anomalies 4 perinatal infections 1 congenital talipes equinovarus 1 cardiac malformation
Sangle et al[65]	Case series	6	5 SLE 1 WG	RTX	8-22 mo prior to C	4 healthy term delivery (3 SLE, 1 WG) 1 preterm low birth weight (SLE) 1 esophageal atresia (SLE)
Pendergraft et al[66]	Case report	1	Autoimmune vasculitis	RTX	7.5 mo prior to C	Spontaneous abortion (Beckwith-Wiedemann Syndrome)

CD: Crohn’s disease; RA: Rheumatoid arthritis; BD: Behcet disease; AS: Ankylosing spondylitis; SpA: Spondyloarthritis; JIA: Juvenile idiopathic arthritis; PsA: Psoriatic arthritis; UndA: Undifferantiated arthritis; JRA: Juvenile rheumatoid arthritis; SLE: Systemic lupus erythematosus; WG: Wegener granulomatosis; AOSD: Adult onset Still’s disease; CAPS: Cryopyrin associated periodic syndromes; INF: İnfliximab; ETA: Etanercept; ADA: Adalimumab; CZP: Certolizumab; GLM: Golimumab; RTX: Rituximab; TCZ: Tocilizumab; C: Conception; T1: First trimester; T2: Second trimester; T3: Third trimester; IUGR: Intrauterine growth restriction; SGA: Small for gestational age; BCG: Bacille Calmette-Guérin; ARDS: Acute respiratory distress syndrome; NR: Not reported; VACTERL: Vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities; UK: Ulcerative colitis; MTX: Methotrexate.