Dose Of Certolizumab Pegol Research Articles

Safety and effectiveness of certolizumab pegol in Japanese patients with rheumatoid arthritis: Up to 3-year results from a postmarketing surveillance study.

To report up to 3-year safety and effectiveness of certolizumab pegol (CZP) in Japanese patients with rheumatoid arthritis from a postmarketing surveillance study. Patients enrolled previously completed 24 weeks of CZP in the 24-week postmarketing surveillance study. Adverse drug reactions (ADRs) were recorded for patients who received ≥1 CZP dose. Effectiveness outcomes were 28-joint Disease Activity Score with erythrocyte sedimentation rate and European Alliance of Associations for Rheumatology response. Week 24-156 safety and Week 0-52 effectiveness data are reported here. A total of 781 patients were enrolled, with 735 and 376 patients evaluated for safety and effectiveness, respectively. Within the safety set, 17.8% (131/735) of patients reported ADRs; 9.4% (69/735) reported serious ADRs. Among patients with history of respiratory, thoracic, and mediastinal disorders, 38.4% (28/73) reported ADRs. The most frequent ADRs were infections and infestations (11.8%; 87/735); skin and subcutaneous tissue disorders (1.9%; 14/735); respiratory, thoracic, and mediastinal disorders (1.6%; 12/735). Mean 28-joint Disease Activity Score with erythrocyte sedimentation rate reduced from 4.6 (Week 0) to 2.8 (Week 52). At Week 52, 51.8% (161/311) of patients achieved European Alliance of Associations for Rheumatology Good response. The long-term safety and effectiveness of CZP in the real-world setting in Japan were consistent with previously reported data; no new safety signals were identified.

Safety and effectiveness of certolizumab pegol in Japanese patients with rheumatoid arthritis: Results from a 24-week post-marketing surveillance study.

To report 24-week safety and effectiveness of certolizumab pegol (CZP) in Japanese patients with rheumatoid arthritis from a post-marketing surveillance study. Enrolled patients were newly receiving CZP. All adverse events (AEs) and adverse drug reactions (ADRs) were recorded for patients who received ≥1 CZP dose. Effectiveness outcomes included: 28-joint Disease Activity Score with erythrocyte sedimentation rate (DAS28-ESR) and European Alliance of Associations for Rheumatology (EULAR) response. Missing data were imputed using the last observation carried forward. 3727 patients were enrolled; safety and effectiveness were evaluated in 3586 and 1794 patients, respectively. 24.9% of patients reported AEs (893/3586), 14.7% reported ADRs (528/3586), 8.3% (298/3586) reported serious AEs and 5.3% (190/3586) reported serious ADRs. Selected serious ADRs of interest: infections (110; 3.1%), tuberculosis (6; 0.2%), interstitial pneumonia (15; 0.4%), malignancy (8; 0.2%), and hepatic function disorder (7; 0.2%). No allergic reactions, autoimmune disease, cardiac failure, demyelinating diseases, or pancytopenia were reported. Mean DAS28-ESR reduced from 4.8 (baseline) to 3.4 (final evaluation). At final evaluation, 34.7% of patients achieved EULAR good response. These real-world safety and effectiveness results were consistent with previously reported data, with no new safety signals identified. Long-term, real-world CZP safety and effectiveness data are needed.

Efficacy and Safety of Certolizumab Pegol in Japanese Patients with Generalized Pustular Psoriasis and Erythrodermic Psoriasis: 52-Week Results.

IntroductionWe report an exploratory analysis of the efficacy and safety of certolizumab pegol (CZP) in Japanese patients with generalized pustular psoriasis (GPP) and erythrodermic psoriasis (EP) (NCT03051217).MethodsPatients ≥ 20 years with GPP or EP were randomized 1:1 to open-label CZP 400 mg every 2 weeks (Q2W) or 200 mg Q2W (400 mg weeks 0/2/4) for 16 weeks; patients who achieved “much improved” or “very much improved” on the Global Improvement Score (GIS; for GPP) or a PASI 50 response (≥ 50% reduction from baseline Psoriasis Area and Severity Index; for EP) continued to week 52. Efficacy outcomes assessed included Clinical Global Impression of Improvement (CGI-I), Dermatology Life Quality Index (DLQI 0/1), and Itch Numeric Rating Scale (INRS 0). GIS and Japanese Dermatological Association (JDA) severity index were assessed in patients with GPP, and PASI and Physician’s Global Assessment (PGA) in patients with EP. Treatment-emergent adverse events (TEAEs) were evaluated through weeks 0–52.ResultsOf 22 patients randomized, 19 completed week 52. At week 16, all reported outcomes improved with both CZP doses and were generally maintained through week 52. At week 52, 6/7 GPP and 12/12 EP patients achieved CGI-I response (“improved” or “remission”). Also, 4/7 GPP and 7/12 EP patients achieved DLQI 0/1; 2/7 GPP and 2/12 EP patients achieved INRS 0. Meanwhile, 6/7 patients with GPP achieved GIS response, and JDA severity index was reduced from baseline. We found that 9/12 and 5/12 patients with EP achieved PASI 90 and PGA 0/1, respectively. Overall, three serious TEAEs were reported in three CZP 400 mg Q2W-treated patients.ConclusionCZP treatment over 16 weeks improved the signs and symptoms of GPP and EP, and improvements were maintained through week 52. No new safety signals were identified.Trial RegistrationClinicalTrials.gov identifier, NCT03051217.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13555-022-00741-x.

Certolizumab Pegol in Japanese Patients with Moderate to Severe Plaque Psoriasis: Effect of Demographics and Baseline Disease Characteristics on Efficacy.

IntroductionWe present certolizumab pegol (CZP) efficacy data across patient demographic and baseline disease characteristic subgroups from a phase 2/3 trial investigating CZP treatment in Japanese patients with moderate to severe plaque psoriasis (PSO; ClinicalTrials.gov identifier: NCT03051217).MethodsPatients were randomised 1:2:2 to placebo once every 2 weeks (Q2W), CZP 400 mg Q2W and CZP 200 mg Q2W (400 mg weeks 0, 2 and 4) for 16 weeks. Patients who achieved ≥ 50% reduction in their baseline Psoriasis Area and Severity Index (PASI 50) score at week 16 continued therapy to week 52. PASI 75/90 (75% and 90% reduction, respectively) and Physician’s Global Assessment (PGA) 0/1 responder rates at weeks 16 and 52 were reported for patient demographic and baseline disease characteristic subgroups, including body mass index (BMI), PASI, disease duration and prior biologic use. Non-responder imputation was used.ResultsOf the randomised patients, 2/26 patients in the placebo group, 47/53 patients in the CZP 400 mg Q2W group and and 39/48 patients in the CZP 200 mg Q2W group completed week 52. In the subgroups evaluated, week 16 efficacy was generally maintained through week 52. At week 52, PASI 75 was achieved by 84.2, 85.7 and 80.0% of patients receiving CZP 400 mg Q2W in the low (15.0–23.7 kg/m2)/intermediate (> 23.7–27.4 kg/m2)/high (> 27.4–47.0 kg/m2) BMI subgroups, respectively, and by 77.8, 70.6 and 69.2%, respectively of patients treated with CZP 200 mg Q2W. PASI 75 at week 52 was achieved by 92.9, 75.0 and 84.2% of patients receiving CZP 400 mg Q2W in the low (12.0–18.0)/intermediate (> 18.0–27.0)/high (> 27.0–67.2) baseline PASI subgroups, respectively, and by 85.0, 58.3 and 68.8% of patients receiving CZP 200 mg Q2W, respectively. Similar responses were observed across other subgroups evaluated for both CZP doses in PASI 75/90 and PGA 0/1.ConclusionClinically meaningful improvements in signs and symptoms of PSO were maintained through week 52 for CZP dosed at 400 mg Q2W or 200 mg Q2W, across patient subgroups. In general, a numerically greater response was observed for patients receiving CZP 400 mg Q2W versus those receiving CZP 200 mg Q2W across patient subgroups.Trial RegistrationClinicalTrials.gov identifier, NCT03051217.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13555-021-00645-2.

Certolizumab Pegol for the Treatment of Moderate to Severe Plaque Psoriasis: 16-Week Results from a Phase2/3 Japanese Study.

IntroductionCertolizumab pegol (CZP), the Fc-free, PEGylated anti-tumor necrosis factor, is approved for the treatment of moderate to severe plaque psoriasis (PSO) in Western countries and in Japan, among other indications.MethodsWe report results from the first 16 weeks of a 52-week phase 2/3 trial of CZP in Japanese patients with PSO. Patients ≥ 20 years with PSO ≥ 6 months (Psoriasis Area and Severity Index [PASI] ≥ 12, body surface area affected ≥ 10%, and Physician’s Global Assessment [PGA] ≥ 3 on a 5-point scale) were randomized 2:2:1 to CZP 400 mg every 2 weeks (Q2W), CZP 200 mg Q2W (400 mg weeks 0/2/4), or placebo Q2W. Outcomes assessed to week 16: PASI 75, PASI 90, PGA 0/1 (Markov chain Monte Carlo), Dermatology Life Quality Index (DLQI 0/1) and Itch Numeric Rating Scale (INRS 0) (non-responder imputation), and DLQI and INRS change from baseline (last observation carried forward). Safety data were reported for patients receiving ≥ 1 dose of study medication through weeks 0–16; adverse events were evaluated using Medical Dictionary for Regulatory Activities version 18.1.ResultsA total of 127 patients were randomized to CZP 400 mg Q2W (N = 53), CZP 200 mg Q2W (N = 48), placebo (N = 26). Week 16 responder rates for CZP 400 mg/200 mg Q2W versus placebo were 87.1%/73.0% versus 7.9% for PASI 75; 75.7%/53.8% versus 0.2% for PASI 90; 66.7%/52.7% versus 0.0% for PGA 0/1 (all p < 0.0001 for both CZP doses versus placebo). Significant improvements in DLQI and INRS were reported at week 16 by patients receiving both CZP doses compared with placebo (p < 0.0001). Incidence of treatment-emergent adverse events within the CZP 400 mg Q2W, CZP 200 mg Q2W, and placebo groups were 326.1, 404.9, and 682.4 per 100 patient-years. No new safety signals were identified compared to previously reported data.ConclusionCZP dosed at 400 mg or 200 mg Q2W was associated with improved PSO signs and symptoms.Trial RegistrationClinicalTrials.gov identifier, NCT03051217.Supplementary InformationThe online version supplementary material available at 10.1007/s13555-021-00494-z.

Long-term safety of certolizumab pegol in plaque psoriasis: pooled analysis over 3 years from three phase III, randomized, placebo-controlled studies.

SummaryBackgroundCertolizumab pegol (CZP) is an Fc‐free, PEGylated anti‐tumour necrosis factor biologic.ObjectivesTo report 3‐year safety data from three phase III trials of CZP in adults with plaque psoriasis.MethodsData were pooled from CIMPASI‐1 (NCT02326298), CIMPASI‐2 (NCT02326272) and CIMPACT (NCT02346240). Included patients had moderate‐to‐severe plaque psoriasis of ≥ 6 months’ duration; had been randomized to CZP 200 mg every 2 weeks (Q2W) (400 mg at weeks 0, 2 and 4) or CZP 400 mg Q2W; and had received at least one dose of CZP with up to 144 weeks of exposure. Treatment‐emergent adverse events (TEAEs) were classified using MedDRA v18·1. Reported incidence rates (IRs) are incidence of new cases per 100 patient‐years (PY).ResultsOver 144 weeks, 995 patients received at least one dose of CZP (exposure: 2231·3 PY); 731 and 728 received at least one dose of CZP 200 mg Q2W (1211·4 PY) and/or 400 mg Q2W (1019·9 PY), respectively. The IR [95% confidence interval (CI)] of TEAEs was 144·9 (135·3–155·0) for all patients, 134·1 (123·2–145·7) for CZP 200 mg Q2W and 158·3 (145·5–171·9) for CZP 400 mg Q2W. The IR (95% CI) of serious TEAEs for all patients was 7·5 (6·4–8·8); the IRs were 6·7 (5·2–8·3) and 8·7 (6·9–10·8) for CZP 200 mg and 400 mg Q2W, respectively. Overall, 3·2% of patients reported serious infections (2·2% within each of the CZP 200 and 400 mg Q2W groups). Overall, there was one case of active tuberculosis, 16 malignancies in 14 patients and seven deaths (two considered treatment‐related). The cumulative IR of TEAEs did not increase over time.ConclusionsNo new safety signals were identified compared with previously reported data. Risk did not increase with longer or higher CZP exposure.

Clinical, Patient-Reported, and Ultrasound Outcomes from an Open-Label, 12-week Observational Study of Certolizumab Pegol in Spanish Patients with Rheumatoid Arthritis with or without Prior Anti-TNF Exposure.

To assess the effectiveness and safety of certolizumab pegol (CZP) in Spanish patients with RA. SONAR (NCT01526434), a 12-week, open-label, prospective, observational, multicenter study. Patients with active RA for ≥3 months, according to ACR criteria, were treated with CZP (400mg at Weeks 0, 2 and 4, then 200mg every 2 weeks). The primary effectiveness endpoint was change from baseline (CFB) in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 12. Other assessments included DAS28(ESR), patient's assessment of arthritis pain (PtAAP-VAS) and Short Form 36-item Health Survey (SF-36) physical component summary (PCS) and mental component summary (MCS). Joint inflammation was investigated using Power Doppler (PD) ultrasound (US), to detect effusion, synovial hypertrophy and synovial PD signal. PDUS outcomes assessed CFB to Week 12 in synovial hypertrophy, effusion and PD signal indices. A total of 77/80 enrolled patients received ≥1 dose of CZP. The 12-week mean reduction from baseline (SD) was -0.6 (0.6) for HAQ-DI and -2.2 (1.5) for DAS28(ESR). PtAAP-VAS was reduced from baseline (mean [SD]: -36.8 [26.8]) and improvements in SF-36 PCS and SF-36 MCS were reported. Synovial hypertrophy, effusion and PD signal indices were reduced from baseline to Week 12. One death was reported during the study. Spanish patients with RA demonstrated improvements in clinical, PDUS and patient-reported outcomes over 12 weeks of CZP treatment. No new safety signals were identified, and the safety profile was in line with previous CZP studies. These results support previous clinical trial findings investigating CZP treatment for active RA.

Clinical, Patient-Reported, and Ultrasound Outcomes from an Open-Label, 12-week Observational Study of Certolizumab Pegol in Spanish Patients with Rheumatoid Arthritis with or without Prior Anti-TNF Exposure

ObjectivesTo assess the effectiveness and safety of certolizumab pegol (CZP) in Spanish patients with RA. Materials and methodsSONAR (NCT01526434), a 12-week, open-label, prospective, observational, multicenter study. Patients with active RA for ≥3 months, according to ACR criteria, were treated with CZP (400mg at Weeks 0, 2 and 4, then 200mg every 2 weeks). The primary effectiveness endpoint was change from baseline (CFB) in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 12. Other assessments included DAS28(ESR), patient's assessment of arthritis pain (PtAAP-VAS) and Short Form 36-item Health Survey (SF-36) physical component summary (PCS) and mental component summary (MCS). Joint inflammation was investigated using Power Doppler (PD) ultrasound (US), to detect effusion, synovial hypertrophy and synovial PD signal. PDUS outcomes assessed CFB to Week 12 in synovial hypertrophy, effusion and PD signal indices. ResultsA total of 77/80 enrolled patients received ≥1 dose of CZP. The 12-week mean reduction from baseline (SD) was −0.6 (0.6) for HAQ-DI and −2.2 (1.5) for DAS28(ESR). PtAAP-VAS was reduced from baseline (mean [SD]: −36.8 [26.8]) and improvements in SF-36 PCS and SF-36 MCS were reported. Synovial hypertrophy, effusion and PD signal indices were reduced from baseline to Week 12. One death was reported during the study. ConclusionsSpanish patients with RA demonstrated improvements in clinical, PDUS and patient-reported outcomes over 12 weeks of CZP treatment. No new safety signals were identified, and the safety profile was in line with previous CZP studies. These results support previous clinical trial findings investigating CZP treatment for active RA.

Effectiveness and safety of 12-month certolizumab pegol treatment for axial spondyloarthritis in real-world clinical practice in Europe.

ObjectivesThe efficacy and safety of certolizumab pegol (CZP), an Fc-free, PEGylated anti-TNF, in axial spondyloarthritis (axSpA) has been established in clinical trial settings. We report CZP effectiveness and safety in European clinical practice in patients with axSpA, including radiographic (r-) and non-radiographic (nr-) axSpA.MethodsCIMAX (NCT02354105), a European non-interventional multicentre prospective study, observed CZP treatment response and safety over 12 months in a real-world axSpA cohort. The primary outcome was change from baseline in BASDAI to week 52, with additional outcomes pertaining to effectiveness and safety. Patients who received ≥1 dose CZP were followed up for adverse events, and those with baseline and ≥1 post-baseline BASDAI assessment were included in effectiveness analyses.ResultsA total of 672 patients (r-axSpA: 469; nr-axSpA: 201; unconfirmed diagnosis: 2) from 101 sites received ≥1 dose of CZP, of whom 564 (r-axSpA: 384; nr-axSpA: 179; unconfirmed: 1) were included in the effectiveness analyses. The mean baseline BASDAI was 6.1 in the overall axSpA population and r-axSpA and nr-axSpA subpopulations. At week 52, the mean (s.d.) change in BASDAI was −2.9 (2.3; n = 439); for r-axSpA and nr-axSpA, it was −2.9 (2.2; n = 301) and −2.8 (2.4; n = 137), respectively (P <0.0001 for all). Similar improvements were seen across other axSpA disease measures. In total, 37.9% (255/672) patients experienced adverse events, and 1.8% (12/672) experienced ≥1 serious adverse events.ConclusionImprovements observed in signs and symptoms of axSpA following one year of CZP treatment in real-world clinical practice were similar to those from previous randomized clinical trials, with no new safety concerns.

Induction of Sustained Clinical Remission in Early Axial Spondyloarthritis Following Certolizumab Pegol Treatment: 48-Week Outcomes from C-OPTIMISE.

IntroductionAchievement of remission is a key treatment goal for patients with axial spondyloarthritis (axSpA). C-OPTIMISE assessed achievement of sustained clinical remission in patients with axSpA, including radiographic (r) and non-radiographic (nr) axSpA, during certolizumab pegol (CZP) treatment, and subsequent maintenance of remission following CZP dose continuation, dose reduction or withdrawal. Here, we report outcomes from the first 48 weeks (induction period) of C-OPTIMISE, during which patients received open-label CZP.MethodsC-OPTIMISE (NCT02505542) was a two-part, multicenter, phase 3b study in adult patients with early axSpA (r-/nr-axSpA), including a 48-week open-label induction period followed by a 48-week maintenance period. Patients with active adult-onset axSpA, < 5 years’ symptom duration, and fulfilling Assessment of SpondyloArthritis international Society classification criteria, were included. During the induction period, patients received a loading dose of CZP 400 mg at weeks 0, 2, and 4, followed by CZP 200 mg every 2 weeks (Q2W) up to week 48. The main outcome of the 48-week induction period was the achievement of sustained clinical remission (defined as an Ankylosing Spondylitis Disease Activity Score [ASDAS] < 1.3 at week 32 and < 2.1 at week 36 [or vice versa], and < 1.3 at week 48).ResultsIn total, 736 patients (407 with r-axSpA, 329 with nr-axSpA) were enrolled into the study. At week 48, 43.9% (323/736) of patients achieved sustained remission, including 42.8% (174/407) of patients with r-axSpA and 45.3% (149/329) with nr-axSpA. Patients also demonstrated substantial improvements in axSpA symptoms, MRI outcomes and quality of life measures. Adverse events occurred in 67.9% (500/736) of patients, of which 6.0% (44/736) were serious.ConclusionsOver 40% of patients with early axSpA achieved sustained remission during 48 weeks of open-label CZP treatment. Additionally, patients across the axSpA spectrum demonstrated substantial improvements in imaging outcomes and quality of life following treatment. No new safety signals were identified.Trial RegistrationNCT02505542.Electronic Supplementary MaterialThe online version of this article (10.1007/s40744-020-00214-7) contains supplementary material, which is available to authorized users.

Efficacy of certolizumab pegol dose escalation in patients who inadequately respond to initial treatment: Results from the CIMPACT trial

Efficacy of certolizumab pegol dose escalation in patients who inadequately respond to initial treatment: Results from the CIMPACT trial

Effectiveness and safety of certolizumab pegol in rheumatoid arthritis patients in Canadian practice: 2-year results from the observational FαsT-CAN study.

Background:The aim of this study was to assess the real-world effectiveness and safety of certolizumab pegol (CZP) in rheumatoid arthritis (RA) patients, and the impact on patients’ productivity, pain, and fatigue, in Canadian practice.Methods:FαsT-CAN, a 2-year prospective, observational study, evaluated CZP use in Canadian adults with moderate to severe, active RA. The primary objective was to assess the proportion of patients achieving 28-joint Disease Activity Scores (DAS28) <2.6 at Week 104. Secondary and additional endpoints assessed the improvements in Patients’ Assessment of Arthritis Pain (PtAAP), fatigue, Health Assessment Questionnaire-Disability Index (HAQ-DI), and the proportion of patients achieving minimal clinically important differences (MCID) in HAQ-DI. Validated arthritis-specific Work Productivity Surveys (WPS-RA) assessed the RA-associated impact on productivity. Incidence of CZP-related treatment-emergent adverse events (TEAEs) was reported for patients receiving ⩾1 dose of CZP (safety set).Results:The full analysis set (baseline DAS28 ⩾ 2.6, ⩾1 dose of CZP and ⩾1 valid post-baseline DAS28 measurement) included 451 of the 546 patients recruited into the study; a total of 229/451 (50.8%) patients completed Week 104. At Week 104, 90/451 (20.0%) patients achieved DAS28 < 2.6. Rapid improvements in disease activity, pain, and fatigue were observed. At Week 104, 66.2% of patients achieved HAQ-DI MCID. Patients employed at Week 104, reported reduced absenteeism, and improved productivity. CZP-related TEAEs were consistent with the known CZP safety profile.Conclusions:CZP was an effective RA treatment in Canadian practice, and no new CZP-related safety signals were identified. The improvements in household and workplace productivity are the first observations in a real-world Canadian setting.

Treatment of Rheumatoid Arthritis with Certolizumab Pegol: Results from PROACTIVE, a Non-Interventional Study in the UK and Ireland.

IntroductionThe objective of this non-interventional study was to investigate the long-term safety and effectiveness of certolizumab pegol (CZP) in patients with rheumatoid arthritis (RA) in the UK and Ireland.MethodsPatients were prescribed CZP at their physicians’ discretion and followed during routine clinical practice for up to 88 weeks. DAS28(ESR) response (defined as at least a 1.2-point reduction from baseline) was measured in the full analysis set (FAS) at week 12, and patients were categorized by week 12 responder status in all subsequent analyses. The primary outcome was DAS28(ESR) response at week 78. Secondary outcomes included change from baseline in DAS28(ESR), HAQ-DI, and RADAI scores at week 78, and EULAR response at week 78. Adverse drug reactions (ADRs) were recorded for all patients who received at least one dose of CZP.ResultsA total of 149 patients were enrolled, of whom 111 (74.5%) formed the FAS. At week 12, 80 patients (72.1%) were DAS28(ESR) responders and 31 (27.9%) non-responders. Compared to non-responders, a greater proportion of week 12 responders had a DAS28(ESR) response at week 78 (43.8% versus 22.6%). Improvements in DAS28(ESR), HAQ-DI, and RADAI scores were also greater on average among week 12 responders, as was the proportion of patients meeting EULAR criteria. Overall, 9 patients (6.1%) experienced 13 ADRs during the study.ConclusionThese data demonstrate the safety and effectiveness of CZP in adult patients with RA treated during routine clinical practice in the UK and Ireland.Trial RegistrationClinicalTrials.gov identifier, NCT01288287.FundingUCB Pharma.Electronic supplementary materialThe online version of this article (10.1007/s12325-018-0758-1) contains supplementary material, which is available to authorized users.

Using Patient Feedback to Optimize the Design of a Certolizumab Pegol Electromechanical Self-Injection Device: Insights from Human Factors Studies.

IntroductionWe incorporated patient feedback from human factors studies (HFS) in the patient-centric design and validation of ava®, an electromechanical device (e-Device) for self-injecting the anti-tumor necrosis factor certolizumab pegol (CZP).MethodsHealthcare professionals, caregivers, healthy volunteers, and patients with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, or Crohn’s disease participated in 11 formative HFS to optimize the e-Device design through intended user feedback; nine studies involved simulated injections. Formative participant questionnaire feedback was collected following e-Device prototype handling. Validation HFS (one EU study and one US study) assessed the safe and effective setup and use of the e-Device using 22 predefined critical tasks. Task outcomes were categorized as “failures” if participants did not succeed within three attempts.ResultsTwo hundred eighty-three participants entered formative (163) and validation (120) HFS; 260 participants performed one or more simulated e-Device self-injections. Design changes following formative HFS included alterations to buttons and the graphical user interface screen. All validation HFS participants completed critical tasks necessary for CZP dose delivery, with minimal critical task failures (12 of 572 critical tasks, 2.1%, in the EU study, and 2 of 5310 critical tasks, less than 0.1%, in the US study).ConclusionCZP e-Device development was guided by intended user feedback through HFS, ensuring the final design addressed patients’ needs. In both validation studies, participants successfully performed all critical tasks, demonstrating safe and effective e-Device self-injections.FundingUCB Pharma.Plain Language SummaryPlain language summary available on the journal website.Electronic supplementary materialThe online version of this article (10.1007/s12325-017-0645-1) contains supplementary material, which is available to authorized users.

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

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...

Evaluating Transfer of Certolizumab Pegol and Polyethylene Glycol into Breast Milk [28J

INTRODUCTION: Breastfeeding women receiving anti-TNFs for chronic inflammatory disease face concerns surrounding their potential transfer into breast milk. CRADLE was the first sponsored study to evaluate certolizumab pegol (CZP) concentrations in breast milk and estimate CZP Average Daily Infant Dose. METHODS: CRADLE (NCT02154425) studied lactating mothers (≥6 weeks postpartum) receiving CZP. After ≥3 CZP doses, breast milk samples were collected across 1 dosing period (14 days for 200 mg Q2W; 28 days for 400 mg Q4W). Optimal analytical methods were developed to determine CZP and total polyethylene glycol (PEG) levels in breast milk. RESULTS: 18 CZP-treated mothers were screened, and 17 entered the sampling period: 16 on 200 mg Q2W and 1 on 400 mg Q4W. 77/137 (56%) samples had no measurable CZP in breast milk. For 4/17 mothers, all samples were below LLQ. Estimated Average Daily Infant Dose was 0‒0.0104 mg/kg/day; median relative infant dose (RID): 0.125%. PEG was undetectable in 134/137 samples (3 had indeterminate results upon retesting). Infants of CZP-exposed mothers had a safety profile consisting of events occurring in unexposed infants of similar age. CONCLUSION: CZP was undetectable in 56% of breast milk samples. When detectable, CZP concentrations were &lt; 3xLLQ (&lt; 1% plasma concentration observed with therapeutic dose), indicating no/minimal CZP transfer from plasma to breast milk. RID was below 0.5% of maternal dose &lt; 10% is considered unlikely to be of clinical concern. No transfer of PEG was observed. CZP absorption by infants via breast milk is unlikely, due to its low oral bioavailability and Fc-free structure. These findings are reassuring and support continuation of CZP treatment during breastfeeding.

Long-Term Maintenance of Certolizumab Pegol Safety and Efficacy, in Combination with Methotrexate and as Monotherapy, in Rheumatoid Arthritis Patients

IntroductionThe safety and efficacy of certolizumab pegol (CZP) 400 mg every 4 weeks (Q4W) monotherapy (FAST4WARD/NCT00548834) and in combination with methotrexate (MTX) (014/NCT00544154) in active rheumatoid arthritis (RA) has been published previously. This report outlines final long-term outcomes from the open-label extension (OLE) study (015/NCT00160693), which enrolled patients from these randomized controlled trials (RCTs).MethodsPatients who withdrew from or completed the 24-week 014/FAST4WARD RCTs were enrolled and received CZP 400 mg Q4W with/without MTX. Exposure-adjusted event rates (ER) per 100 patient-years (PYs) of adverse events (AEs) and serious AEs (SAEs) were reported for all patients receiving ≥1 dose of CZP in RCTs or OLE (N = 427) between first CZP dose and up to 24 weeks after last CZP dose or study withdrawal. Efficacy assessments included clinical (ACR20/50/70 response rates, TJC, SJC) and patient-reported outcomes (HAQ-DI, PtGADA, pain, fatigue) to week 304 (5.8 years) in the CZP intent-to-treat population. SDAI and CDAI outcomes were analyzed post hoc. Outcomes for CZP monotherapy and CZP+MTX combination-therapy were compared.ResultsGlobally, ERs of AEs and SAEs were 408.1 and 25.2 per 100 PY, respectively. Eleven patients had AEs leading to death (ER 0.6). Improvements in clinical and patient-reported outcomes during the 24-week RCTs were maintained to week 304, and were similar between all subpopulations.ConclusionsThe longest exposure duration to date with CZP 400 mg Q4W treatment confirmed the safety profile observed in previous studies. Initial improvements in signs and symptoms of RA, including PROs, were maintained in both CZP monotherapy and CZP + MTX combination-therapy patients. Trial registration: ClinicalTrials.gov identifier, NCT00160693. Funding: UCB Pharma.Electronic supplementary materialThe online version of this article (doi:10.1007/s40744-017-0060-8) contains supplementary material, which is available to authorized users.

Evaluating Transfer of Certolizumab Pegol into Breast Milk: Results from CRADLE, a Prospective, Postmarketing, Multicenter Pharmacokinetics Study

Introduction: Women with chronic inflammatory diseases face uncertainty regarding the safety of the use of biologics during breastfeeding. Currently, limited and non-validated data exist on potential transfer of anti-TNFs into breast milk. CRADLE was the first sponsored study designed to evaluate certolizumab pegol (CZP) concentrations ([C]) in breast milk, and to estimate the average daily infant dose. Methods: CRADLE (NCT02154425) was a safety and pharmacokinetic study of lactating mothers (≥6 weeks postpartum) receiving commercial CZP for an approved indication. Decision to treat with CZP and to breastfeed was made independently of study participation. At steady-state (≥3 CZP doses), breast milk samples were collected at days 0, 2, 4, 6, 8, 10, 12, 14 (±28) from each mother across 1 dosing period. A highly sensitive CZP-specific ELISA was developed (validated in milk; LLQ=0.032μg/mL, 10-fold lower than assay used in CZP PK studies1). CZP stability in milk was confirmed. Results: 18 CZP-treated mothers were screened and 17 entered the sampling period; 16 on CZP 200mg Q2W; 1 on CZP 400mg Q4W (5 CD; 12 RA/SpA; Table 1). Samples from 4/17 mothers had no measurable CZP in breast milk; 13/17 had quantifiable levels at any time point (highest [C]: 0.076μg/mL; Figure 1). Estimated average daily infant dose ranged 0-0.0104mg/kg/day; median relative infant dose (RID, calculated 2 post hoc by Dr Hale): 0.15%. The infants of mothers exposed to CZP had a safety profile consisting of events occurring in unexposed infants of similar age (Table 2).Figure 1Table 1: Baseline Characteristics of Mothers and InfantsTable 2: Summary of Adverse Events from the Safety Set during the CRADLE Study (from Screening to Safety Follow-Up)Conclusion: Using the highly sensitive assay, 56% of samples were below LLQ while remainder had maximum CZP [C] < 3 times LLQ ( < 1% of expected plasma [C] of a therapeutic dose 1) indicating minimal to no transfer of CZP from plasma to breast milk. RID was below 0.5% of maternal dose ( < 10% unlikely to be of concern to infant wellbeing2). Additionally, CZP absorption by infants via breast milk is unlikely due to its Fc-free molecular structure3 and low oral bioavailability. These findings imply that continuation of CZP treatment is compatible with breastfeeding. 1. Lacroix BD. Gastroenterol 2010;138:S163-4 2. Bennett PN. Drugs and Human Lactation. 1996 3. Israel EJ. Immunology 1997;92:69-74 Funding: UCB Pharma We are indebted to the mothers and their infants for their altruistic participation. We thank the nurses, investigator teams, Nicole Hurst (PPD) and acknowledge Amanda Golembesky and Gerry Parker, UCB Pharma.

Impact of Certolizumab Pegol on Patient‐Reported Outcomes in Patients With Axial Spondyloarthritis

ObjectivePatient‐reported outcomes (PROs) provide an opportunity to collect important information relating to patient well‐being, which is often difficult for physicians to measure (e.g., quality of life, pain, fatigue, and sleep). Here we evaluate the effects of certolizumab pegol (CZP) on PROs during the 24‐week, double‐blind phase of the RAPID axial spondyloarthritis (SpA) trial, a phase 3 trial of axial SpA patients, including both ankylosing spondylitis (AS) and nonradiographic axial SpA patients.MethodsA total of 325 patients with active axial SpA were randomized 1:1:1 to placebo, CZP 200 mg every 2 weeks, or CZP 400 mg every 4 weeks. The primary end point was the Assessment of SpondyloArthritis International Society criteria for 20% improvement in disease activity response at week 12, and has been reported previously. PROs included total back pain, nocturnal back pain, a daily pain diary, the Sleep Problems Index II (SPI) domain of the Medical Outcomes Study (MOS) Sleep Scale, fatigue, the Ankylosing Spondylitis Quality of Life (ASQOL) measure, and the Short Form 36‐item (SF‐36) health survey physical component summary (PCS), mental component summary (MCS), and domains.ResultsPatients treated with CZP reported significant improvements from week 1 for nocturnal back pain (placebo −0.6, CZP 200 mg every 2 weeks −1.9, and CZP 400 mg every 4 weeks −1.6; P < 0.001) and ASQOL (placebo −1.0, CZP 200 mg every 2 weeks −2.3, and CZP 400 mg every 4 weeks −1.9; P < 0.05) compared with placebo, while significant improvements in total back pain were seen from day 2. Patients treated with both CZP dosing regimens also had significantly greater improvements in fatigue, MOS‐SPI, SF‐36 PCS, MCS, and domains compared with placebo. Improvements were similar in both AS and nonradiographic axial SpA patients.ConclusionBoth CZP dosing schedules rapidly improved patient well‐being, as measured by PROs, including pain, fatigue, sleep, SF‐36, and ASQOL in both AS and nonradiographic axial SpA patients.

Effect of certolizumab pegol over 96 weeks in patients with psoriatic arthritis with and without prior antitumour necrosis factor exposure

ObjectivePrevious reports of RAPID-PsA (NCT01087788) demonstrated efficacy and safety of certolizumab pegol (CZP) over 24 weeks in patients with psoriatic arthritis (PsA), including patients with prior antitumour necrosis factor (TNF)...