Improving The Sensitivity and Specificity of A Bioanalytical Assay for The Measurement of Certolizumab Pegol

Smeraglia, John; Silva, John-Paul; Jones, K.

doi:10.4155/bio-2017-0124

Cited by 5 publications

(6 citation statements)

References 23 publications

(32 reference statements)

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“…Furthermore, to enhance the accuracy of CZP measurement, a new electrochemiluminescence assay was developed. 22 This technology offered significantly improved specificity and sensitivity over the ELISA previously used by Mahadevan et al and Förger et al . 20 23 24 …”

Section: Discussionmentioning

confidence: 97%

“…In addition, at an LLOQ of 0.032 μg/mL, the new assay is over 10 times more sensitive than the previous ELISA. 22 Consequently, this assay enabled us to provide much more accurate data regarding placental transfer of CZP, which can be translated with greater confidence into evidence-based clinical practice.…”

Section: Discussionmentioning

confidence: 99%

“…CZP concentrations were measured using an electrochemiluminescence immunoassay validated in human plasma. 22 The assay was developed for optimal sensitivity and specificity: CZP was captured by a TNF-coated multiarray electrode and detected with an anti-PEG antibody, prior to reading on a MESO SCALE DISCOVERY platform (MSD; Rockville, MD, USA). 22 The assay is CZP-specific and >10 times more sensitive (lower limit of quantification [LLOQ] 0.032 μg/mL) than the previous ELISA used in other CZP PK studies.…”

Section: Methodsmentioning

confidence: 99%

“… 22 The assay was developed for optimal sensitivity and specificity: CZP was captured by a TNF-coated multiarray electrode and detected with an anti-PEG antibody, prior to reading on a MESO SCALE DISCOVERY platform (MSD; Rockville, MD, USA). 22 The assay is CZP-specific and >10 times more sensitive (lower limit of quantification [LLOQ] 0.032 μg/mL) than the previous ELISA used in other CZP PK studies. 20 23 24 Anti-CZP antibodies were measured using a previously validated ELISA (samples were positive if anti-CZP antibody levels were >2.4 units/mL).…”

Section: Methodsmentioning

confidence: 99%

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Lack of placental transfer of certolizumab pegol during pregnancy: results from CRIB, a prospective, postmarketing, pharmacokinetic study

et al. 2017

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ObjectivesThere is a need for effective and safe treatment during pregnancy in women with chronic inflammatory diseases. This study evaluated placental transfer of certolizumab pegol (CZP), an Fc-free anti-tumour necrosis factor drug, from CZP-treated pregnant women to their infants.MethodsCRIB was a pharmacokinetic (PK) study of women ≥30 weeks pregnant receiving commercial CZP for a locally approved indication (last dose ≤35 days prior to delivery). Blood samples were collected from mothers, umbilical cords and infants at delivery, and infants again at weeks 4 and 8 post-delivery. CZP plasma concentrations were measured with a highly sensitive and CZP-specific electrochemiluminescence immunoassay (lower limit of quantification 0.032 μg/mL).ResultsSixteen women entered and completed the study. Maternal CZP plasma levels at delivery were within the expected therapeutic range (median [range] 24.4 [5.0–49.4] μg/mL). Of the 16 infants, 2 were excluded from the per-protocol set: 1 due to missing data at birth and 1 due to implausible PK data. Of the remaining 14 infants, 13 had no quantifiable CZP levels at birth (<0.032 μg/mL), and 1 had a minimal CZP level of 0.042 μg/mL (infant/mother plasma ratio 0.0009); no infants had quantifiable CZP levels at weeks 4 and 8. Of 16 umbilical cord samples, 1 was excluded due to missing data; 3/15 had quantifiable CZP levels (maximum 0.048 μg/mL).ConclusionsThere was no to minimal placental transfer of CZP from mothers to infants, suggesting lack of in utero foetal exposure during the third trimester. These results support continuation of CZP treatment during pregnancy, when considered necessary.Trial registration numberNCT02019602; Results.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Lack of placental transfer of certolizumab pegol during pregnancy: results from CRIB, a prospective, postmarketing, pharmacokinetic study

et al. 2017

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“…CZP concentration in breast milk was measured using an electro-chemiluminescence immunoassay, in which CZP was captured by a TNF-coated multiarray electrode and detected with an anti-PEG antibody, prior to reading on a Meso Scale Discovery (MSD; Rockville, Maryland, USA) platform. 25 The assay is CZP-specific and, due to the technical advantages of the MSD methodology (high sensitivity, large dynamic range, small sample volume 26 27 ), >10 times more sensitive (lower limit of quantification [LLOQ]: 0.032 µg/mL) than the previous ELISA used in other CZP PK studies. 11 28 29 The assay was validated in milk; CZP stability in milk was confirmed.…”

Section: Methodsmentioning

confidence: 99%

Minimal to no transfer of certolizumab pegol into breast milk: results from CRADLE, a prospective, postmarketing, multicentre, pharmacokinetic study

et al. 2017

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BackgroundWomen with chronic inflammatory diseases face uncertainty regarding the safety of biologics during breast feeding. CRADLE was the first industry-sponsored study to evaluate certolizumab pegol (CZP) concentrations in human breast milk and estimate average daily infant dose (ADID) of maternal CZP.MethodsCRADLE (NCT02154425) was a pharmacokinetic study of lactating mothers receiving CZP. After ≥3 CZP doses, breast milk samples were collected across one dosing period (14 days for 200 mg every 2 weeks [Q2W]; 28 days for 400 mg every 4 weeks [Q4W]). Optimal analytical methods were developed to determine CZP and polyethylene glycol (PEG) levels in breast milk. ADID and relative infant dose (RID) were estimated. Safety events in mothers and infants were assessed.Results19 CZP-treated mothers were screened; 17 entered the sampling period: 16 on 200 mg Q2W, 1 on 400 mg Q4W. 77/137 (56%) breast milk samples had no measurable CZP. For 4/17 mothers, all samples were below the lower limit of quantification (LLOQ). Estimated ADID was 0–0.0104 mg/kg/day; median RID: 0.15%. PEG was undetectable in 134/137 samples (results could not be determined in three samples). Infants of CZP-exposed mothers had a safety profile consistent with that of unexposed similar-age infants.ConclusionWhen quantifiable, CZP concentrations were <3× LLOQ (<1% plasma concentration observed with therapeutic dose), indicating no/minimal CZP transfer from plasma to breast milk. RID was 0.15% of maternal dose; <10% is considered unlikely to be of clinical concern. No PEG transfer was observed. CZP absorption by infants via breast milk is unlikely due to its low oral bioavailability and Fc-free molecular structure. These findings are reassuring and support continuation of CZP treatment during breast feeding.Trial registration numberNCT02154425; Results.

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Thermoelectrically Activated Chips for Optical Sensing: A portable diagnostic platform for improved immunoassay specificity

et al. 2019

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Immunological‐based assays have been widely used in diagnostic applications since the initial description of the methodology for the detection of human insulin. However, the development of immunoassays has been hindered by inherent cross‐reactivities between antibodies (Ab) and closely related antigens (Ag) that contribute to false‐positive results. In this work, we utilize temperature‐dependent immunoassay measurements to distinguish between closely related flavivirus antigens—obviating the need for a laborious development effort to ensure assay specificity. A novel platform named Thermoelectrically Activated Chips for Optical Sensing (TACOS), consisting of a miniaturized well plate overlaid on an array of thermoelectric cooling or heating pixels, enables simultaneous immunoassay measurements at different binding temperatures. The efficacy of Ab‐Ag complex formation correlates with the affinity between the Ab‐Ag pair, which is in turn dependent on the binding temperature controlled by the TACOS platform. In this study, Ab‐Ag complex formation over a temperature range is demonstrated as a unique identifier of Ab‐Ag complex composition. We contend that TACOS circumvents the need for extensive and expensive immunoassay developments and therefore enables future diagnostic tests suitable for far‐forward field applications.

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Improving The Sensitivity and Specificity of A Bioanalytical Assay for The Measurement of Certolizumab Pegol

Cited by 5 publications

References 23 publications

Lack of placental transfer of certolizumab pegol during pregnancy: results from CRIB, a prospective, postmarketing, pharmacokinetic study

Lack of placental transfer of certolizumab pegol during pregnancy: results from CRIB, a prospective, postmarketing, pharmacokinetic study

Minimal to no transfer of certolizumab pegol into breast milk: results from CRADLE, a prospective, postmarketing, multicentre, pharmacokinetic study

Thermoelectrically Activated Chips for Optical Sensing: A portable diagnostic platform for improved immunoassay specificity

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