Certolizumab Pegol In Patients Research Articles

Long-Term Durability of Certolizumab Pegol in Patients with Rheumatoid Arthritis Over 5 Years: An Analysis of Pooled Clinical Trial Data.

There is a paucity of data on how patient characteristics may affect the long-term durability of certolizumab pegol (CZP) in patients with rheumatoid arthritis (RA). This study therefore aimed to investigate CZP durability and reasons for discontinuation over 5years between different subgroups of patients with RA. Data were pooled from 27 clinical trials in RA patients. Durability was defined as the percentage of patients randomized to CZP at baseline who were still on CZP treatment at a given timepoint. Post hoc analyses of clinical trial data on CZP durability and reasons for discontinuation among different patient subgroups were conducted using Kaplan-Meier curves and Cox proportional hazards modeling. Patient subgroups included: age (18- < 45/45- < 65/ ≥ 65years), gender (male/female), prior tumor necrosis factor inhibitor (TNFi) use (yes/no), and disease duration (< 1/1- < 5/5- < 10/ ≥ 10years). Among 6927 patients, the durability of CZP was 39.7% at 5years. Patients aged ≥ 65years had a 33% greater risk of CZP discontinuation than patients 18- < 45years (hazard ratio [95% confidence interval]: 1.33 [1.19-1.49]) and patients with prior TNFi use had a 24% greater risk of discontinuing CZP than patients without (1.24 [1.12-1.37]). Conversely, greater durability was observed among patients who had a baseline disease duration of ≥ 1year. Durability did not differ in the gender subgroup. Of the 6927 patients, the most common reason for discontinuation was inadequate levels of efficacy (13.5%); followed by adverse events (11.9%); consent withdrawn (6.7%); lost to follow-up (1.8%); protocol violation (1.7%); other reasons (9.3%). CZP durability was comparable with durability data on other bDMARDs in RA patients. Patient characteristics that were associated with greater durability included younger age, TNFi-naïvety, and disease duration ≥ 1year. Findings may be helpful in informing clinicians on a patient's likelihood of discontinuing CZP, based on their baseline characteristics.

Certolizumab Pegol Treatment in Patients with Axial-Spondyloarthritis-Associated Acute Anterior Uveitis: a Narrative Review.

BackgroundAcute anterior uveitis (AAU) affects up to 40% of patients with axial spondyloarthritis (axSpA). An effective treatment for patients with axSpA that reduces the risk of AAU flares while also targeting axial symptoms is therefore highly desirable. Tumor necrosis factor inhibitors (TNFis) have been shown effective for treatment of axSpA and AAU occurrence, with guidelines conditionally recommending treating patients with axSpA and associated AAU with TNFi monoclonal antibodies. To date, most available data on the impact of TNFis on AAU in axSpA are from observational, open-label studies without parallel comparator arms. However, there is a growing body of evidence describing the impact of the TNFi certolizumab pegol (CZP) on the incidence of axSpA-associated AAU.ObjectiveOur objective was to collate data pertaining to the impact of CZP in axSpA-associated AAU in patients across the full axSpA spectrum.MethodsData were obtained from four industry-supported phase 3 and 4 clinical trials (C-VIEW, C-axSpAnd, C-OPTIMISE, and RAPID-axSpA). To supplement these data, a targeted literature review was performed through searches of MEDLINE, Embase, and reference lists.ResultsAvailable data from 1467 patients from the C-VIEW, C-axSpAnd, C-OPTIMISE, and RAPID-axSpA trials show CZP to be effective in AAU in patients across the full axSpA spectrum, reducing AAU flares when compared with placebo or pretreatment period. No differences in AAU outcomes were reported when stratified by axSpA subgroup age or sex. The targeted literature review identified six further studies of CZP in spondyloarthritis-associated AAU, only one of which was specific to axSpA.ConclusionCZP was effective in reducing AAU incidence in clinical trials with patients with axSpA. The targeted literature review, however, highlighted that there remains a paucity of data beyond these trials. Data from comparative studies would further enhance the body of evidence on the effects of CZP in patients with axSpA who develop AAU.Graphical abstract Supplementary InformationThe online version contains supplementary material available at 10.1007/s40744-022-00486-1.

AB0479 LONGTERM RETENTION RATE OF CERTOLIZUMAB PEGOL IN AXIAL SPONDYLOARTHRITIS IS HIGHER: DATA FROM TURKBIO

Background:Choosing the best treatment strategy for a patient is one of the most difficult issues in modern rheumatology, as there are various factors affecting drug therapy in chronic diseases, such as efficacy, safety, and compliance. Physicians take care of long-term retention rate and responses for discontinuation of candidate drug.Objectives:The purpose of this study to assess the drug survival of certolizumab pegol (CZP) in patients with axial spondyloarthritis (ax-SpA) and to identify the predictors and reasons for discontinuation.Methods:Data on patient characteristics, demographics, diagnosis, duration of disease, treatment and outcomes have been collected since 2011 in Turkish Biologic (TURKBIO) Registry. By the end of December 2020, 410 ax-SpA patients received CZP and were included. Kaplan Meier plot was used for drug survival analysis. Cox regression analysis was performed to evaluate the predictor associated with drug survival.Results:During the median 54 months follow-up, 92 (22.4%) patients discontinued the CZP treatment. The reasons for discontinuation: ineffectivity was 58.7% (n=54), adverse events was 6.5%, pregnancy was 3.3% and surgery was 4.3%. The baseline characteristics of patients continue with CZP and discontinuation due to ineffectiveness were shown in the Table 1. Patients who discontinued CZP had higher HAQ, BASFI and BASDAI values. Moreover, they were more co-treated with NSAIDs and csDMARDs. At the month 36, retention rate of CZP was 71.5% in patients with ax-SpA (Figure 1).Conclusion:Real life experience from this nationwide TURKBIO registry show higher long-term retention rate of CZP in ax-SpA. Higher baseline disease activity and functional limitation predict discontinuation of CZP. Adding NSAIDs and csDMARDs to the treatment of the patient with poor prognosis cannot increase retention rates.Figure 1Drug survival of CZP in patients with Ax-SpATable 1.Baseline characteristics of ax-SpA patients who continue and discontinue CZPAll patients (n=410)Continue to CZP (n=318)Discontinue to CZP* (n=54)pFemales, n (%)185 (49,7)157 (49,4)28 (51,9)0,736Age, years42 (34-49)41 (34-49)45 (34-54)0,064Symptom duration, years11 (7-17)11 (6-16)12 (8,5-20)0,054HLA-B27, n (%)150 (63,8)129 (64,5)21 (60)0,609Previous bDMARDs, n (%)Adalimumab54 (14,5)42 (13,2)12 (22,2)0,082Etanercept53 (14,2)40 (12,6)13 (24,1)0,025Golimumab11 (3)7 (2,2)4 (7,4)0,060Infliximab39 (10,5)35 (11)4 (7,4)0,425Co-treated drugs, n (%)NSAID206 (55,4)169 (53,1)37 (68,5)0,036Methotrexate35 (9,4)22 (6,9)13 (24,1)&lt;0,001Sulphasalazine61 (16,4)40 (12,6)21 (38,9)&lt;0,001Leflunomide5 (1,3)2 (0,6)3 (5,6)0,023ESH, mm/h21,5 (10-37)21 (10-37)23 (10-34)0,999CRP, mg/dl7 (3-20)7 (3-20)7 (3-22)0,727HAQ0,63 (0,25-0,94)0,5 (0,25-0,88)0,75 (0,38-1,25)0,009BASFI21 (7-45)20,5 (6-41)31 (13-58)0,011BASDAI30,5 (13-52)30 (12-50)43 (23-61,5)0,002ASDAS2,7 (1,8-3,7)2,7 (1,8-3,6)2,9 (2,3-4)0,062*Discontinue due to ineffectivity.

PMS21 Cost Analysis of Work and Household Productivity Improvements with Certolizumab Pegol in Patients with NON-Radiographic Axial Spondyloarthritis in Spain

PMS21 Cost Analysis of Work and Household Productivity Improvements with Certolizumab Pegol in Patients with NON-Radiographic Axial Spondyloarthritis in Spain

PBI14 Budget IMPACT Analysis of a Reduced Maintenance Dose of Certolizumab Pegol in Patients with Axial Spondyloarthritis in the United Kingdom

The C-OPTIMISE trial (NCT02505542) demonstrated that reduced certolizumab pegol (CZP) maintenance dose (RMD, 200mg every 4 weeks [Q4W]) is a possible regimen for adults with axial spondyloarthritis (axSpA) in sustained remission. This analysis explored the budget impact of introducing CZP RMD for axSpA in the UK. The eligible population of UK axSpA patients (prevalence 0.13%) treated with tumour necrosis factor (TNF) inhibitors (17.3%, Wilmington database 2019) was estimated and updated quarterly over five years (2020–2024). Drug acquisition (including branded and biosimilar products), administration and direct medical management costs (GBP, 2020) were applied to the estimated market share for each treatment. No discounting was applied. A reference scenario considering CZP full maintenance dose (FMD; 200mg Q2W) with 0.5% CZP annual market share growth was compared to a scenario where the RMD was applied to 44% of CZP patients assumed to have achieved sustained remission after one year. A marginally higher risk of disease flare on RMD (21%) compared to FMD (16%) was accounted for. An annual all-cause discontinuation rate of 10% was applied to all treatments. Assuming a market share of 10% for CZP at baseline (1,177 patients), CZP RMD in eligible patients generated a £13.34 million saving in CZP drug costs between 2021 and 2024 (-19.95% vs. CZP FMD). Incremental flare costs were marginal (£6,074; +0.11% vs. FMD). Overall, net savings with RMD were £13.33 million, out of £627.17 million total spend in the FMD scenario. Scenario analysis of RMD suggested that cost savings were still realised within reasonable CZP market share uptake assumptions. CZP RMD for axSpA patients in sustained remission led to net savings compared to continuing FMD regimen in the UK, due to lower overall cost of treatment despite a marginal direct cost increase associated with marginally higher risk of disease flare.

14998 Reductions in absolute PASI over 144 weeks of treatment with certolizumab pegol in patients with plaque psoriasis: Pooled analysis from two phase 3 trials (CIMPASI-1 and CIMPASI-2)

Background: Certolizumab pegol (CZP) is an Fc-free, PEGylated anti–tumor necrosis factor. Here, we report the proportions of patients with moderate to severe plaque psoriasis (PSO) achieving clinically relevant absolute PASI thresholds over 144 weeks’ CZP treatment.

Three-year clinical outcomes in patients with rheumatoid arthritis treated with certolizumab pegol: results from the observational ECLAIR study

To describe the long-term effectiveness and safety of certolizumab pegol in patients with moderate-to-severe rheumatoid arthritis (RA) in a real-world setting in France. ECLAIR was a 3-year longitudinal, prospective, observational, multicentre study. The primary objective was to describe the EULAR response after 1 year of certolizumab pegol treatment. Other endpoints included DAS28, clinical disease activity index, health assessment questionnaire disability index, fatigue assessment scale, patient's assessment of arthritis pain, patient and physician global assessments of disease activity, patient quality of life, and long-term safety. A total of 792 patients were enrolled, of whom 776 comprised the safety set, and 733 the full analysis set. In the full analysis set, 559, 469 and 430 patients had a 12-, 24- and 36-month visit, respectively. This included 378, 296 and 246 patients still receiving certolizumab pegol at these visits. The percentage of EULAR responders was 75.3% (305/405 patients with an available EULAR response) at 12, 76.5% (261/341) at 24, and 79.6% (226/284) at 36 months. Among those still receiving certolizumab pegol, the percentage of EULAR responders was 81.7% (237/290) at 12, 81.1% (185/228) at 24, and 87.3% (158/181) at 36 months. Sustained improvements were observed in other effectiveness outcomes. Overall, 45.1% (350/776) of patients experienced 776 adverse drug reactions. No new safety signals were identified. This is the first prospective, observational study of an anti-TNF treatment in France. The results confirm the effectiveness and safety profile of certolizumab pegol treatment in patients with RA in a real-world setting.

Experience of a Performance-Based Risk-Sharing Arrangement for the Treatment of Rheumatoid Arthritis With Certolizumab Pegol

ObjectivesTo describe the process and results of the implementation of a performance-based risk-sharing arrangement for the use of certolizumab pegol (Cimzia) in patients with rheumatoid arthritis (RA), based on rational pharmacotherapy. MethodsIn 2014, the area of Management of Drugs and Supplies of the health maintenance organization of the Hospital Italiano de Buenos Aires signed a performance-based risk-sharing arrangement with Montpellier Laboratory for the use of certolizumab pegol in patients with RA. The laboratory would reimburse the hospital the cost of the first 10 doses of the drug if an optimal clinical response was not achieved (difference greater than or equal to 1.2 in the Disease Activity Score 28 with erythrocyte sedimentation [Δ DAS28 ESR] measured at the beginning and at the end), or if the patient presented with an adverse drug reaction, during the first 12 weeks of treatment. ResultsForty patients with RA were included between September 2014 and January 2018. Thirty-six patients completed 12 weeks of treatment, of which 25 (69.4 %) had an optimal clinical response (Δ DAS28 ESR ≥ 1.2). The laboratory reimbursed the hospital 116 doses of certolizumab pegol, corresponding to 12 patients (12 of 40, 30%). Eleven of them did not reach the optimal clinical response, and 1 presented with an adverse drug reaction. ConclusionsThe performance-based risk-sharing arrangement proved to be a useful tool to optimize the resources of the healthcare payer and contributed to the collection of scientific evidence in real-life patients.

P092 Induction of clinical remission with certolizumab pegol in patients with ulcerative colitis who are not responders in Mexican population

BACKGROUND: The TNF alpha inhibitor have revolutionized the treatment of inflammatory bowel disease (IBD), both in ulcerative colitis (UC) and in Crohn's disease (CD), achieving not only clinical remission even the healing of the affected mucosa. In our population, 70% of patients with IBD are diagnosed as UC and 30% CD. Currently, there are only 2 biologics approved for UC: infliximab and adalimumab. One third of patients will not respond to anti-TNF after induction and up to 50% of them will lose efficacy in the first year. Certolizumab pegol (CZP) has shown therapeutic efficacy in CD. In our country there are no studies that evaluate its use in UC. The aim of this work is to assess the efficacy of CZP in patients with UC with secondary failure to 2 anti-TNF alpha. METHODS: Study proof of concept. Six patients with UC diagnosis referred to our hospital center due to secondary failure to 2 anti-TNF alpha were studied. The severity of the disease was staged according to the Mayo score. Prior authorization of the patient for treatment with CZP, we administered it, at a dose of 400 mg subcutaneously at week 0, 2 and every 4 weeks, for 12 weeks. Clinical response was reviewed at 8 and 12 weeks after the beginning of the application of the biological and also endoscopically at 8 and 12 weeks. RESULTS: 50% corresponded to female sex with a female: male 1 to 1. The median age was: 52.50 [23–63] years. Of the 6 patients, 5 had left colitis and 1 had pancolitis. 4 patients fulfilled criteria of Mayo for severe activity and 2 with moderate activity. 4 patients with an endoscopic subscore Mayo 2 and 2 patients with endoscopic subscore Mayo 3. At the baseline measurement, 50% (3) had a normal CRP and 100% had albumin within normal parameters. At 8 weeks of follow-up, 50% of patients entered clinical remission by Mayo score. 4 patients had an endoscopic subscore May 1 or lower. At 12 weeks of biological application, the same results were observed. By laboratory it was observed at 12 weeks that 83.3% had CRP within normal parameters and 66.7% had normal albumin. No secondary events were observed during the 12 weeks of treatment. CONCLUSION(S): In this work proof of concept, CZP seems to be an option in patients with UC who have had secondary failure to other anti-TNF; however, because of the small size of the sample, a prospective and randomized study is required to confirm these findings. The present work does not have conflict of interests.

The Potential Benefits of Certolizumab Pegol in Patients with Concurrent Psoriatic Arthritis and Chronic Plaque Psoriasis: A Case Series and Review of the Literature.

IntroductionWe review the literature evaluating certolizumab in psoriasis and report our experience of treatment outcomes in a joint dermatology and rheumatology clinic.MethodsPatients with concomitant psoriatic arthritis (PsA) and psoriasis who had been commenced on certolizumab were included within our retrospective review. Data was collected for patient demographics, Patient Area and Severity Index (PASI), Dermatology Life Quality Index (DLQI) and previous treatments. The literature was systematically searched using Pubmed and Scopus.ResultsVery recent results from the CIMPASI-1 and CIMPASI-2 studies have demonstrated the high efficacy of certolizumab in the treatment of psoriasis at both week 16 and 48. Pooled results from these studies showed a PASI75 at week 16 and week 48 of 82% and 83.6% respectively, in the certolizumab 400 mg group. In our cohort of eight patients (two female; six male; median age 49 and mean PASI of 20.8) all had failed at least two systemic non-biologic agents. Objective improvements were observed in seven patients, with five achieving PASI90 and two demonstrating either PASI75 or PASI50.ConclusionCertolizumab is efficacious in both psoriasis and PsA, including in patients who are biologic failures, and could be considered as an alternative treatment modality.

Therapeutic effect of certolizumab pegol in patients with rheumatoid arthritis in daily clinical practice: A single-center, retrospective study

Therapeutic effect of certolizumab pegol in patients with rheumatoid arthritis in daily clinical practice: A single-center, retrospective study

A pooled subanalysis of the efficacy of certolizumab pegol in patients with self-reported psoriatic arthritis in ongoing phase 3 psoriasis studies (CIMPASI-1, CIMPASI-2, and CIMPACT)

A pooled subanalysis of the efficacy of certolizumab pegol in patients with self-reported psoriatic arthritis in ongoing phase 3 psoriasis studies (CIMPASI-1, CIMPASI-2, and CIMPACT)

Accounting for Pharmacokinetic Variability of Certolizumab Pegol in Patients with Crohn's Disease.

Certolizumab pegol is an effective biologic for patients with Crohn's disease (CD). Individual differences in certolizumab pegol apparent clearance (CL/F) affect exposure and possibly efficacy. A previously developed population pharmacokinetic (PK) model did not account for dynamic changes in clinical parameters during therapy. The aim of this study was to refine the existing PK model to capture the time-varying influence of covariates. Data collected from 2157 Crohn's disease patients in nine studies were analyzed using nonlinear mixed-effects modeling software (NONMEM). Certolizumab pegol concentration-time data were described by a one-compartment PK model with first-order absorption, and one-compartment disposition with linear, time-dependent elimination using antidrug antibody (ADAb) concentration as a continuous variable. The final dataset consisted of 12,926 analyzable records. Parameter estimates were absorption rate constant1.83/day, CL/F 0.527L/day, and apparent volume of distribution (V/F) 8.33L. ADAb concentration (2.5-214units/mL) increased the median CL/F by 142-174%. For a typical patient, body weight (46.8-100.5kg) increased the median CL/F and V/F from 82 to 120%. Albumin (32-48g/L) decreased and C-reactive protein (0.5-54.0mg/L) increased the median CL/F from 123 to 85% and from 83 to 113%, respectively. Between-patient variability of CL/F was 19.6%. By incorporating time-varying covariates, this population PK model reduces between-patient variability on CL/F estimates, and the relative influence of ADAb can now be assessed. As Crohn's disease patient covariates are often time-dependent, this model is more reflective of patient drug exposure with sustained treatment.

Scintigraphic detection of TNF-driven inflammation by radiolabelled certolizumab pegol in patients with rheumatoid arthritis and spondyloarthritis

BackgroundBiologicals are the cornerstone for many treatment algorithms in inflammatory arthritis. While tumour necrosis factor (TNF) inhibitors may achieve important responses in ∼50% of patients with rheumatoid arthritis (RA) and...

Modeling of the clinical and economic impact of a risk-sharing agreement supporting a treat-to-target strategy in the management of patients with rheumatoid arthritis in France

Objectives: To evaluate the cost-effectiveness of a Treat-to-Target strategy with certolizumab pegol in patients with rheumatoid arthritis in the context of a pay-for-performance agreement in which medication costs are refunded in case of discontinuation during the first 3 months of treatment.Methods: The Treat-to-Target strategy consisted of a systematic switch to second-line tumor necrosis factor (TNF)α inhibitor in case of an unmet ACR50 response at 3 months compared to current routine clinical practice. A reference cohort treated first-line with certolizumab pegol according to current practice without systematic switching was considered as the comparator. A decision-tree model was constructed to estimate clinical outcome (health assessment questionnaire-disability index or HAQ-DI score), time spent in ACR50 response (ACR 50), and direct costs of treatment over a 2-year period. HAQ scores were derived from American College of Rheumatology 50 (ACR50) responses. All TNFα inhibitors were assumed to have equivalent efficacy and tolerability. Costs were estimated at 2013 French retail prices (date of the pay-for-performance agreement).Results: The mean duration of an ACR50 response was 1.23 years in the Treat-to-Target strategy certolizumab pegol cohort vs 0.98 years in the reference cohort, resulting in a mean gain in HAQ at 24 months of 0.117. The Treat-to-Target strategy with a mix of TNFα inhibitors as second-line therapy was more expensive than the reference strategy in absolute terms, but this difference was entirely offset by the pay-for-performance agreement. The Treat-to-Target strategy was, thus, cost-neutral over a 2-year period after the payback of CZP cost for patients not achieving the target at 3 months.Conclusions: In the context of a pay-for-performance agreement, the management of patients with rheumatoid arthritis using a Treat-to-Target strategy with certolizumab pegol in first line is dominant compared to standard use of this drug in the French setting in 2013.

Safety Profile of Certolizumab Pegol in Patients with Immune-Mediated Inflammatory Diseases: A Systematic Review and Meta-Analysis.

Certolizumab pegol (CZP), an anti-tumor necrosis factor PEGylated Fab' fragment of a humanized monoclonal antibody, is currently approved for treatment of some immune-mediated inflammatory diseases (IMIDs). To our knowledge, no systematic review and meta-analysis evaluating the overall safety profile of CZP has been performed. The objective of this systematic review was to assess the adverse event (AE) patterns of CZP versus a control in patients with IMIDs. A systematic literature search was performed using PubMed/MEDLINE, EMBASE, the Cochrane Library, and the FDA database for clinical trials up to March 2014. Eligible studies were those that compared the safety profile of CZP to a control group in patients with IMIDs. The following data were extracted: number of patients experiencing AEs, serious AEs (SAEs), adverse drug reactions (ADRs), withdrawals due to AEs, fatal AEs, infectious AEs and SAEs, upper respiratory tract infections, injection-site reactions, neoplasms, and tuberculosis. A total of 2023 references were identified and 18 randomized controlled trials were included. The main pooled risk ratios of CZP-treated versus control patients were as follows: AEs 1.09 (95% confidence interval, CI 1.04-1.14), SAEs 1.50 (95% CI 1.21-1.86), ADRs 1.20 (95% CI 1.03-1.39), infectious AEs 1.28 (95% CI 1.13-1.45), infectious SAEs 2.17 (95% CI 1.36-3.47), and upper respiratory tract infections 1.34 (95% CI 1.15-1.57). Safety data on CZP suggest an overall favorable tolerability profile, with infections being the most common AE. However, CZP-treated patients had a twofold higher risk of infectious SAEs than control patients. Large observational studies and data from national registries are needed to detect rare AEs, which might occur after long-term exposures to CZP.

Population pharmacokinetic analysis of certolizumab pegol in patients with Crohn's disease.

Certolizumab pegol (CZP), an anti–tumor necrosis factor α agent, is an effective therapy for Crohn's disease (CD). A population pharmacokinetic (PK) analysis of subcutaneously administered CZP was performed using data from 2157 CD patients from 9 separate studies. The aim was to determine which covariates influence the disposition of CZP. The final CZP population PK model consisted of a baseline, first‐order absorption, and 1‐compartment disposition. CZP antibodies were treated as a structural model covariate and caused apparent clearance (CL/F) to increase from 0.685 to 2.74 L/day. Body surface area (BSA) influenced both CL/F and apparent volume of distribution (V/F) in a linear fashion; both parameters increased by more than 53% and 49%, respectively, across the range of BSA measurements in the data. Albumin influenced CZP CL/F in a nonlinear fashion; CL/F decreased from 1.05 to 0.613 L/day with increasing albumin concentrations in antibody‐negative patients. C‐reactive protein (CRP) had a borderline influence and CL/F increased by more than 20% across the range of CRP measurements in the data set. Race had a minor influence on V/F. The determined covariates' impact on CZP disposition may be of clinical utility in CZP therapy of CD patients when the PK/pharmacodynamic relationship becomes available.

Efficacy of switching to certolizumab pegol in patients with rheumatoid arthritis who have multiple swollen joints with treatment of biologic DMARDs

Efficacy of switching to certolizumab pegol in patients with rheumatoid arthritis who have multiple swollen joints with treatment of biologic DMARDs

PMS73 - Long-Term Maintenance of Improvements in Patient-Reported Outcomes With Certolizumab Pegol in Patients With Axial Spondyloarthritis, Including Ankylosing Spondylitis and Non-Radiographic Axial Spondyloarthritis: 96-Week Results of the Rapid-Axspa Study

PMS73 - Long-Term Maintenance of Improvements in Patient-Reported Outcomes With Certolizumab Pegol in Patients With Axial Spondyloarthritis, Including Ankylosing Spondylitis and Non-Radiographic Axial Spondyloarthritis: 96-Week Results of the Rapid-Axspa Study

Clinical Correlates and Pharmacokinetic Parameters of Certolizumab Pegol Predicted by Modeling in Patients With Crohn’s Disease

Introduction: To characterize clinical correlates relevant for pharmacokinetics (PK) of certolizumab pegol (CZP) in patients with Crohn’s disease (CD) via a population PK analysis. Methods: Plasma CZP concentration time data were pooled from 9 clinical studies investigating subcutaneously administered CZP in patients with moderate to severe CD, and were subject to a population PK analysis using nonlinear mixed effects modeling (NONMEM). A co-variate analysis was performed to identify factors that impact the PK parameters. Results: Plasma concentration-time data were available from 2,157 patients with 13,561 quantifiable CZP plasma concentrations. The data were adequately described by a one-compartment, first-order absorption disposition model. CZP anti-drug antibodies were found to influence clearance (CL) of CZP as well as between-subject variability. The estimate of baseline concentrations was also influenced. The results of the co-variate analysis showed that body surface area (BSA), albumin concentrations, and Creactive protein (CRP) at baseline were the most clinically relevant co-variates. Furthermore, BSA influenced both CL and volume of distribution (Vd) in a linear fashion; these parameters increased by over 53% and 49% across the range of BSA measurements. Albumin was found to influence the CL of CZP in a nonlinear fashion, with a steep change in CL with increasing albumin concentrations below 41 g/L (Figure 1). Ethnicity was found to influence Vd, but not all the race categories were statistically significant or met relevant clinical criteria.Figure 1: The impact of albumin concentrations at baseline on the clearance of certolizumab pegol.Conclusion: The clinically and statistically relevant co-variates affecting CL of CZP were anti-CZP antibodies, BSA, albumin, and CRP at baseline. Vd was influenced by BSA and ethnicity. Disclosure - Janet Wade is an employee SGS Exprimo and a consultant to UCB Pharma. Ruth Oliver, Gerry Parker, and Gordana Kosutic are employees of UCB Pharma and have stocks and stock options. Brian Feagan is a Speakers Bureau Member for: Abbott/AbbVie, JnJ/Janssen, Takeda, Warner-Chilcott, UCB Pharma, Consulting Fee/Advisory Board: Abbott/AbbVie, Actogenix, Albireo Pharma, Amgen, Astra Zeneca, Avaxia Biologics Inc., Axcan, Baxter Healthcare Corp., Boehringer-Ingelheim, Bristol-Myers Squibb, Calypso Biotech, Celgene, Elan/Biogen, EnGene, Ferring Pharma, Roche/Genentech, GiCare Pharma, Gilead, Given Imaging Inc., GSK, Ironwood Pharma, Janssen Biotech (Centocor), JnJ/Janssen, Kyowa Kakko Kirin Co Ltd., Lexicon, Lilly, Merck, Millennium, Nektar, Novonordisk, Pfizer, Prometheus Therapeutics and Diagnostics, Protagonist, Receptos, Salix Pharma, Serono, Shire, Sigmoid Pharma, Synergy Pharma Inc., Takeda, Teva Pharma, Tillotts, UCB Pharma, Vertex Pharma, Warner-Chilcott, Wyeth, Zealand, Zyngenia. Contracted Research: Abbott/AbbVie, Amgen, Astra Zeneca, Bristol-Myers Squibb (BMS), Janssen Biotech (Centocor), JnJ/Janssen, Roche/Genentech, Millennium, Pfizer, Receptos, Santarus, Sanofi, Tillotts, UCB Pharma.