CRADLE was the first industry-sponsored clinical study to evaluate Cimzia concentrations in human breast milk.¹ 

137 mature breast milk samples were collected from 17 lactating mothers. Mothers received Cimzia on either the 2-weekly dose (200mg every 2 weeks) or the 4-weekly dose regimen (400mg every 4 weeks). After at least three doses, when plasma Cimzia concentrations were considered at a steady-state, mature breast milk samples were collected over a single dosing period - every other day for a 2-week period. Women in the 4-weekly dose regimen provided an additional sample on day 28.¹

This study found minimal transfer of Cimzia from the plasma into the breast milk, with an infant receiving, on median RID 0.15% (relative infant dose) of the maternal dose. Adverse events in the mothers were consistent with the known Cimzia safety profile, and the events observed in infants were consistent with those in unexposed infants of similar age.¹ 

The level of Cimzia ingested by the suckling infant is minimal. The adverse events recorded in mothers were consistent with the current Cimzia safety profile, while events in infants being consistent with those occurring in unexposed infants of similar age. Therefore, this study indicates that the continuation of Cimzia treatment is compatible with breastfeeding.¹ 

All 17 mothers who entered the sampling period completed the study (no missed visits) and 100% of planned samples were collected;¹ Day 0 of the sampling period was ≥6 weeks post-delivery and when the patient was on an established Cimzia dose regimen.¹

Minimal to no transfer of Cimzia into breast milk: results from CRADLE, a prospective, post-marketing, multicentre, pharmacokinetic study^a,1

CZP, Cimzia; CZP Q2W, 200mg Cimzia every 2 weeks; CZP Q4W, 400mg Cimzia every 4 weeks

This study did not include Psoriasis (PsO) patients nor patients on a CIMZIA 400 mg Q2W maintenance dose.

a Cimzia concentrations measured using an electro-chemiluminescence immunoassay validated in human plasma; >10 times more sensitive than the previous ELISA, enzyme-linked immunoassay, used in other Cimzia pharmacokinetics studies.

Cimzia concentrations less than three times lower limit of quantification (LLOQ); Highest Cimzia concentration was 0.076 µg/mL, less than three times the LLOQ: 0.032 µg/mL.

Median estimated Average daily infant dose (ADID) was 0.003503 mg/kg/day (range 0 to 0.0104 mg/kg/day); Median relative infant dose was 0.15% (range 0.04% to 0.30%) of the maternal dose.¹

ADID

Adapted from Clowse MEB, et al. Ann Rheum Dis 2017

This study included also patients with Crohn’s disease. Cimzia is not approved to treat CD in the UK

The safety analysis included all mothers who received at least one dose of CZP and the infants of all mothers who participated in the study. The safety follow-up period extended up to 5 weeks (±5 days) after the final sample was collected. AEs in mother-infant pairs were not necessarily associated temporally.

*See study design above.

†SF, includes one screen failure: mother discontinued from study due to AE of herpes zoster during screening period.

‡Breast abscess during screening period, which resolved prior to sampling.

Adapted from Clowse MEB, et al. Ann Rheum Dis 2017

CRADLE Study: Key Safety Profile Trial Data

Overall, 10 mothers (55.6%) experienced 14 AEs, and 8 infants (47.1%) experienced 11 AEs; 5 AEs in four mothers were considered treatment related; 2 (11.1%) upper respiratory tract infection; and 1 each (5.6%) of herpes zoster, CD, Crohn's Disease flare and pneumonia; Nasopharyngitis in one infant (5.9%) of mild intensity was considered drug related based on known Cimzia safety profile.¹