Pregnancy outcomes in patients with psoriasis, psoriatic arthritis, or axial spondyloarthritis receiving ixekizumab

Figures & data

Table 1. Overview of clinical trials in psoriasis, psoriatic arthritis, and axial spondyloarthritis for which safety data was reported in the Eli Lilly Global Safety Database through 22 March 2019.

	Study name	Phase	Study design	N
Psoriasis	I1F-MC-RHAG	1	R, DB, placebo-controlled, dose escalation study	46
	I1F-MC-RHBU	1	Single arm, OL, drug interaction study	28
	I1F-MC-RHAJ	2	R, DB, placebo-controlled, dose-ranging design with an optional OL extension design and additional optional EP with an OL design	142
	I1F-MC-RHBL (UNCOVER-A)	3	R, OL, two drug delivery devices (prefilled syringe, auto-injector)	204
	I1F-JE-RHAT (UNCOVER-J)	3	Single-arm, OL	91
	I1F-US-RHBO	3	R, OL	12
	I1F-EW-RHBZ	3	R, OL, active comparators: Fumaric acid esters, MTX	162
	I1F-MC-RHAZ (UNCOVER-1)	3	R, DB, placebo-controlled	1296
	I1F-MC-RHBA (UNCOVER-2)	3	R, DB, placebo-controlled, active comparator: ETN	1224
	I1F-MC-RHBC (UNCOVER-3)	3	R, DB, placebo-controlled, LTE period, active comparator: ETN	1346
	I1F-MC-RHBP (IXORA-P)	3	R, DB	1257
	I1F-MC-RHBS (IXORA-S)	3	R, blinded, active comparator: UST	302
	I1F-MC-RHBQ (IXORA-Q)	3	R, DB, placebo	149
Psoriatic arthritis	I1F-MC-RHAP (SPIRIT-P1)	3	R, DB, placebo-controlled, active reference: ADA	417
	I1F-MC-RHBE (SPIRIT-P2)	3	R, DB, placebo-controlled	363
	I1F-MC-RHBF (SPIRIT-P3)	3	R, OL period followed by DB withdrawal period, placebo	394
	I1F-MC-RHCF (SPIRIT-H2H)	4	R, OL, parallel-group, H2H vs. ADA	566
Axial spondyloarthritis	I1F-MC-RHBV (COAST-V)	3	R, DB, placebo-controlled, bDMARD-naive patients with r-axSpA, active reference: ADA	341
	I1F-MC-RHBW (COAST-W)	3	R, DB, placebo-controlled, TNFi-experienced patients with r-axSpA	316
	I1F-MC-RHBX (COAST-X)	3	R, DB, placebo-controlled, bDMARD-naïve patients with non-r-axSpA	305
	I1F-MC-RHBY (COAST-Y)	3	R, LTE including DB placebo-controlled 40-week randomized withdrawal-retreatment period	750

ADA: adalimumab; bDMARD: biologic disease-modifying antirheumatic drug; DB: double-blind; EP: extension period; ETN: etanercept; H2H: head-to-head; LTE: long-term extension; MTX: methotrexate; N: number of patients; OL: open-label; R: randomization; r-axSpA: radiographic axial spondyloarthritis; TNFi: tumor necrosis factor inhibitor; UST: ustekinumab.

Figure 1. Time of maternal exposure to ixekizumab and pregnancy outcomes by age group for patients in clinical trials.

Table 2. Exposure information and outcomes for maternal ixekizumab exposure pregnancies (N = 99)^a captured in the Eli Lilly Global Safety Database^b.

	Clinical trials (n = 58)	Post-marketing surveillance (n = 41)
Age^c (years), mean ± SD	30.22 ± 6.25	31.37 ± 4.94
Indication^d
Psoriasis	52 (89.7)	31 (75.6)
Psoriatic arthritis	4 (6.9)	1 (2.4)
Axial spondyloarthritis	2 (3.5)	0 (0)
Other/unknown	0 (0)	9 (22.0)
Exposure timing^d
First trimester	56 (96.6)	19 (46.3)
All trimesters	0 (0)	2 (4.9)^e
Trimester unknown	2 (3.5)	20 (48.8)
Ixekizumab discontinuation status^d
Discontinued^f	56 (96.6)	30 (73.2)
No discontinuation	2 (3.5)	4 (9.8)
Unknown	0 (0)	7 (17.1)
Pregnancy outcome^d
Live birth	28 (48.3)	11 (26.8)
Non-live birth^h	0 (0.0)	0 (0.0)
Spontaneous abortion or miscarriage	11 (19.0)	3 (7.3)
Elective termination	13 (22.4)	4 (9.8)
Lost to follow-up or unknown	6 (10.3)	23 (56.1)
Live births^g
Full term	22 (78.6)	5 (45.5)
Pre-term	5 (17.9)	1 (9.1)
Term unknown	1 (3.6)	5 (45.5)
Infant outcome
Congenital malformation	0	1^i

SD: standard deviation.

^a99 pregnancies were recorded for 99 patients.

^bAll values are reported as n (%) unless otherwise specified.

^cAge was not available for six women in a post-marketing setting.

^dPercentages were calculated using the total number of pregnancies in the relevant setting as the denominator.

^eFetal outcome unknown in one patient, the other infant had no fetal abnormalities or complications during pregnancy.

^fIncludes one patient who discontinued ixekizumab during the first trimester, but later restarted ixekizumab just before giving birth.

^gPercentages were calculated using the number of live births in the relevant setting as the denominator.

^hStillbirth and infant death within 28 days post-partum.

ⁱFollow-up information was only available for one live-birth infant, who had a congenital malformation (esophageal atresia with tracheoesophageal fistula and hypospadias).