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CRADLE

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Study design

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

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Efficacy

This study found minimal transfer of Cimzia from the plasma into the breast milk, with an infant receiving, on average, 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 studya,1

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

This study did not include Psoriasis (PsO) patients.

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

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

Median estimated 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: Average daily infant dose.

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

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Safety profile

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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, 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.

CRADLE Study: Key Safety 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 flare and pneumonia; Nasopharyngitis in one infant (5.9%) of mild intensity was considered drug related based on known Cimzia safety profile.1

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Conclusion

The findings of the CRADLE study are reassuring and support the continuation of Cimzia treatment during breast feeding for women with rheumatoid arthritis, radiographic axial spondyloarthritis, non-radiographic axial spondyloarthritis, and psoriatic arthritis.

Since certolizumab pegol is a protein that is degraded in the gastrointestinal tract after oral administration, the absolute bioavailability is expected to be very low in a breastfed infant.2

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References

  1. Clowse MEB, et al. Ann Rheum Dis 2017;76(11) 1890-1896.
  2. Cimzia® Summary of Product Characteristics. [Accessed April 2021].
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Because we're in this together...

Report adverse events

Adverse events should be reported. Reporting forms and information can be found at www.yellowcard.mhra.gov.uk and hpra.ie/homepage/about-us/report-an-issue.

Adverse events should also be reported to UCB Pharma Ltd Email: UCBCares.UK@ucb.com and UCBCares.IE@ucb.com.

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Date of preparation: May 2021
IE-P-CZ-AS-2100019