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Psoriasis is a chronic inflammatory condition for which eleven FDA-approved biologic therapies are approved. Over the past decade, studies have documented the higher efficacy of IL-17 and IL-23 inhibitors for the treatment of psoriasis compared to the TNF-alpha inhibitors and ustekinumab, an IL-12/23 inhibitor. Despite this, there remains an important role for the use of TNF-alpha inhibitors and ustekinumab in the treatment of psoriasis. Here, we review how considerations of infection and malignancy risk, patient demographics, treatment resistance, and co-morbidities may make certain TNF-alpha inhibitors or ustekinumab an excellent choice for therapy in particular patient subgroups.

BackgroundCertolizumab pegol (CZP) is an Fc-free, PEGylated anti-tumor necrosis factor biologic.ObjectivesTo report 3-year outcomes from the CIMPACT (NCT02346240) phase 3, CZP in moderate to severe plaque psoriasis, randomized controlled trial.MethodsAdults were randomized 3:3:3:1 to CZP 200 mg every other week (Q2W), CZP 400 mg Q2W, etanercept biweekly or placebo. At Week 16, CZP- and etanercept-treated PASI 75 responders were re-randomized to CZP 200 mg Q2W, CZP 400 mg Q4W, CZP 400 mg Q2W or placebo for maintenance treatment; PASI 75 non-responders entered an open-label escape CZP 400 mg Q2W arm. Patients entering the open-label extension (OLE; Weeks 48-144) from blinded treatment received CZP 200 mg Q2W.ResultsDouble-blinded results have been reported previously. 261 patients received 200 mg Q2W upon OLE entry. PASI 75 response was maintained in patients continuing 200 mg Q2W treatment through Weeks 16-144 (Week 144: 96.2%). In patients dosed down at Week 48 (double-blinded 400 mg to 200 mg Q2W), PASI 75 decreased (Week 48: 98.7%; Week 144: 85.9%). In patients who received placebo through Weeks 16-48, PASI 75 response decreased (Week 48: 60.4%), then increased following Week 48 switch to 200 mg Q2W (Week 144: 95.1%). 48 and 36 patients initially randomized to 200 and 400 mg Q2W, respectively, were Week 16 PASI 75 non-responders and entered the escape arm; at Week 144, 71.8% and 78.2% achieved PASI 75. No new safety signals were identified.ConclusionsResponse to CZP was durable over three years; no new safety signals were identified.

Objectives: In patients with rheumatoid arthritis (RA), high disease activity impairs fertility outcomes and increases the risk of adverse pregnancy outcomes. The aim of this study was to determine the feasibility of a modern treatment approach, including treat-to-target (T2T) and the prescription of tumour necrosis factor (TNF) inhibitors, in patients with RA with a wish to conceive or who are pregnant. Methods: Patients were derived from the Preconception Counseling in Active RA (PreCARA) cohort. Patients with a wish to conceive or who are pregnant were treated according to a modified T2T approach, in which the obvious restrictions of pregnancy were taken into account. Results of the PreCARA study were compared with results of the Pregnancy-induced Amelioration of Rheumatoid Arthritis (PARA) study, a historic reference cohort on RA during pregnancy. Patients in the PARA cohort were treated according to the standards of that time (2002-2010). Differences in disease activity over time between the two cohorts were tested using a linear mixed model. Results: 309 patients with RA were included in the PreCARA study, 188 children were born. 47.3% of the patients used a TNF inhibitor at any time during pregnancy. Mean disease activity over time in the PreCARA cohort was lower than in the reference cohort (p<0.001). In the PreCARA cohort, 75.4% of the patients were in low disease activity (LDA) or remission before pregnancy increasing to 90.4% in the third trimester, whereas in the PARA cohort, these percentages were 33.2% and 47.3%, respectively. Conclusions: This first study on a modern treatment approach in pregnant patients with RA shows that LDA and remission are an attainable goal during pregnancy, with 90.4% of patients achieving this in the third trimester.

Biosimilars are increasingly adopted to improve affordability of biologics. An effective introduction of biosimilars requires an understanding of patient acceptance of these agents. We performed a cross-sectional study of 132 patients with rheumatoid arthritis prior to the introduction of biosimilar switching or prescribing in this cohort. Despite being unfamiliar with biosimilars, most patients are willing to accept biosimilar medicines if recommended by their rheumatologist. Patient concerns about biosimilar uptake mainly focus on concerns about its efficacy. There is a significant correlation between patient attitudes towards biosimilar and generic medicines.Copyright © 2020 Royal Australasian College of Physicians

Biosimilars are increasingly adopted to improve affordability of biologics. An effective introduction of biosimilars requires an understanding of patient acceptance of these agents. We performed a cross-sectional study of 132 patients with rheumatoid arthritis prior to the introduction of biosimilar switching or prescribing in this cohort. Despite being unfamiliar with biosimilars, most patients are willing to accept biosimilar medicines if recommended by their rheumatologist. Patient concerns about biosimilar uptake mainly focus on concerns about its efficacy. There is a significant correlation between patient attitudes towards biosimilar and generic medicines.Copyright © 2020 Royal Australasian College of Physicians

ObjectiveThe natural history of nonradiographic axial spondyloarthritis (SpA) is incompletely characterized, and there are concerns that nonsteroidal antiinflammatory drugs provide inadequate disease control in patients with active disease. This study was undertaken to investigate the effects of certolizumab pegol (CZP), an anti-tumor necrosis factor treatment, in patients with nonradiographic axial SpA with objective signs of inflammation.MethodsIn this ongoing parallel-group double-blind study, adults with active disease were recruited from 80 centers in Australia, Europe, North America, and Taiwan, and were randomized 1:1 to receive placebo or CZP (400 mg at weeks 0, 2, and 4, followed by 200 mg every 2 weeks) in addition to nonbiologic background medication (NBBM). Switching to open-label CZP (or other biologic) or making background medication changes was permitted at any point during the trial, although changes before week 12 were discouraged. The primary end point was the proportion of patients achieving major improvement (MI) (i.e., a ≥2.0-point decrease in the score from baseline or achievement of the lowest possible score [0.6]) in the Ankylosing Spondylitis Disease Activity Score (ASDAS) at week 52.ResultsA total of 317 patients were randomized to receive placebo plus NBBM (n = 158) or CZP plus NBBM (n = 159). ASDAS-MI at week 52 was achieved in 47.2% (75 of 159) of CZP plus NBBM patients, which was significantly greater (P < 0.0001) than the 7.0% (11 of 158) of placebo plus NBBM patients in whom ASDAS-MI was achieved. Of the placebo plus NBBM patients, 60.8% (96 of 158) switched to open-label treatment before week 52 compared to 12.6% (20 of 159) of the CZP plus NBBM patients.ConclusionAdding CZP to background medication is superior to adding placebo in patients with active nonradiographic axial SpA. These results indicate that remission in nonradiographic axial SpA treated without biologics occurs infrequently, demonstrating the need for treatment bey

[ES] Objetivo: Comparar la eficacia farmacológica y la seguridad del Certolizumab Pegol (CZP) con la del Tocilizumab (TCZ) en el tratamiento de la artritis reumatoide (AR) activa moderada a grave en el adulto en términos de respuesta ACR20 y de incidencia de eventos adversos, respectivamente. Material y métodos: Para llevar a cabo la revisión sistemática se realizaron dos búsquedas de ensayos clínicos en la base de datos PubMed, una sobre el CZP y otra sobre el TCZ. Se extrajeron las variables establecidas a partir de los textos completos de los estudios seleccionados y considerados de calidad según las directrices del grupo CONSORT. Resultados: En la búsqueda sistemática se obtuvieron un total de 19 ensayos clínicos, 8 sobre el CZP y 11 sobre el TCZ. Posteriormente, se completó el trabajo con otros tipos de publicaciones, tres libros y la página web de la Agencia Española de Medicamentos y Productos Sanitarios (AEMPS). Discusión: El TCZ a dosis de 8 mg/kg (posología recomendada) en monoterapia consiguió un mayor porcentaje de respuestas ACR20 en comparación con CZP 200 mg (posología recomendada) en monoterapia; mientras que en combinación con metotrexato (MTX) u otros Fármacos Antirreumáticos Modificadores de la Enfermedad (FAME), el porcentaje de respuesta de ambos fue similar. Ambos fármacos mostraron un buen perfil de seguridad y no existen datos que muestren un mayor riesgo atribuible al tratamiento con ninguno de ellos para los pacientes tratados en comparación con la población general. Conclusión: Tanto el CZP como el TCZ son seguros y eficaces para su uso (ya sea en monoterapia o en combinación con FAME) en el tratamiento de la AR moderada a severamente activa, mostrando una ligera superioridad en monoterapia el TCZ frente al CZP a las dosis estudiadas.

[ES] Objetivo: Comparar la eficacia farmacológica y la seguridad del Certolizumab Pegol (CZP) con la del Tocilizumab (TCZ) en el tratamiento de la artritis reumatoide (AR) activa moderada a grave en el adulto en términos de respuesta ACR20 y de incidencia de eventos adversos, respectivamente. Material y métodos: Para llevar a cabo la revisión sistemática se realizaron dos búsquedas de ensayos clínicos en la base de datos PubMed, una sobre el CZP y otra sobre el TCZ. Se extrajeron las variables establecidas a partir de los textos completos de los estudios seleccionados y considerados de calidad según las directrices del grupo CONSORT. Resultados: En la búsqueda sistemática se obtuvieron un total de 19 ensayos clínicos, 8 sobre el CZP y 11 sobre el TCZ. Posteriormente, se completó el trabajo con otros tipos de publicaciones, tres libros y la página web de la Agencia Española de Medicamentos y Productos Sanitarios (AEMPS). Discusión: El TCZ a dosis de 8 mg/kg (posología recomendada) en monoterapia consiguió un mayor porcentaje de respuestas ACR20 en comparación con CZP 200 mg (posología recomendada) en monoterapia; mientras que en combinación con metotrexato (MTX) u otros Fármacos Antirreumáticos Modificadores de la Enfermedad (FAME), el porcentaje de respuesta de ambos fue similar. Ambos fármacos mostraron un buen perfil de seguridad y no existen datos que muestren un mayor riesgo atribuible al tratamiento con ninguno de ellos para los pacientes tratados en comparación con la población general. Conclusión: Tanto el CZP como el TCZ son seguros y eficaces para su uso (ya sea en monoterapia o en combinación con FAME) en el tratamiento de la AR moderada a severamente activa, mostrando una ligera superioridad en monoterapia el TCZ frente al CZP a las dosis estudiadas.

[ES] Objetivo: Comparar la eficacia farmacológica y la seguridad del Certolizumab Pegol (CZP) con la del Tocilizumab (TCZ) en el tratamiento de la artritis reumatoide (AR) activa moderada a grave en el adulto en términos de respuesta ACR20 y de incidencia de eventos adversos, respectivamente. Material y métodos: Para llevar a cabo la revisión sistemática se realizaron dos búsquedas de ensayos clínicos en la base de datos PubMed, una sobre el CZP y otra sobre el TCZ. Se extrajeron las variables establecidas a partir de los textos completos de los estudios seleccionados y considerados de calidad según las directrices del grupo CONSORT. Resultados: En la búsqueda sistemática se obtuvieron un total de 19 ensayos clínicos, 8 sobre el CZP y 11 sobre el TCZ. Posteriormente, se completó el trabajo con otros tipos de publicaciones, tres libros y la página web de la Agencia Española de Medicamentos y Productos Sanitarios (AEMPS). Discusión: El TCZ a dosis de 8 mg/kg (posología recomendada) en monoterapia consiguió un mayor porcentaje de respuestas ACR20 en comparación con CZP 200 mg (posología recomendada) en monoterapia; mientras que en combinación con metotrexato (MTX) u otros Fármacos Antirreumáticos Modificadores de la Enfermedad (FAME), el porcentaje de respuesta de ambos fue similar. Ambos fármacos mostraron un buen perfil de seguridad y no existen datos que muestren un mayor riesgo atribuible al tratamiento con ninguno de ellos para los pacientes tratados en comparación con la población general. Conclusión: Tanto el CZP como el TCZ son seguros y eficaces para su uso (ya sea en monoterapia o en combinación con FAME) en el tratamiento de la AR moderada a severamente activa, mostrando una ligera superioridad en monoterapia el TCZ frente al CZP a las dosis estudiadas.

[ES] Objetivo: Comparar la eficacia farmacológica y la seguridad del Certolizumab Pegol (CZP) con la del Tocilizumab (TCZ) en el tratamiento de la artritis reumatoide (AR) activa moderada a grave en el adulto en términos de respuesta ACR20 y de incidencia de eventos adversos, respectivamente. Material y métodos: Para llevar a cabo la revisión sistemática se realizaron dos búsquedas de ensayos clínicos en la base de datos PubMed, una sobre el CZP y otra sobre el TCZ. Se extrajeron las variables establecidas a partir de los textos completos de los estudios seleccionados y considerados de calidad según las directrices del grupo CONSORT. Resultados: En la búsqueda sistemática se obtuvieron un total de 19 ensayos clínicos, 8 sobre el CZP y 11 sobre el TCZ. Posteriormente, se completó el trabajo con otros tipos de publicaciones, tres libros y la página web de la Agencia Española de Medicamentos y Productos Sanitarios (AEMPS). Discusión: El TCZ a dosis de 8 mg/kg (posología recomendada) en monoterapia consiguió un mayor porcentaje de respuestas ACR20 en comparación con CZP 200 mg (posología recomendada) en monoterapia; mientras que en combinación con metotrexato (MTX) u otros Fármacos Antirreumáticos Modificadores de la Enfermedad (FAME), el porcentaje de respuesta de ambos fue similar. Ambos fármacos mostraron un buen perfil de seguridad y no existen datos que muestren un mayor riesgo atribuible al tratamiento con ninguno de ellos para los pacientes tratados en comparación con la población general. Conclusión: Tanto el CZP como el TCZ son seguros y eficaces para su uso (ya sea en monoterapia o en combinación con FAME) en el tratamiento de la AR moderada a severamente activa, mostrando una ligera superioridad en monoterapia el TCZ frente al CZP a las dosis estudiadas.

ObjectiveThe natural history of nonradiographic axial spondyloarthritis (SpA) is incompletely characterized, and there are concerns that nonsteroidal antiinflammatory drugs provide inadequate disease control in patients with active disease. This study was undertaken to investigate the effects of certolizumab pegol (CZP), an anti-tumor necrosis factor treatment, in patients with nonradiographic axial SpA with objective signs of inflammation.MethodsIn this ongoing parallel-group double-blind study, adults with active disease were recruited from 80 centers in Australia, Europe, North America, and Taiwan, and were randomized 1:1 to receive placebo or CZP (400 mg at weeks 0, 2, and 4, followed by 200 mg every 2 weeks) in addition to nonbiologic background medication (NBBM). Switching to open-label CZP (or other biologic) or making background medication changes was permitted at any point during the trial, although changes before week 12 were discouraged. The primary end point was the proportion of patients achieving major improvement (MI) (i.e., a ≥2.0-point decrease in the score from baseline or achievement of the lowest possible score [0.6]) in the Ankylosing Spondylitis Disease Activity Score (ASDAS) at week 52.ResultsA total of 317 patients were randomized to receive placebo plus NBBM (n = 158) or CZP plus NBBM (n = 159). ASDAS-MI at week 52 was achieved in 47.2% (75 of 159) of CZP plus NBBM patients, which was significantly greater (P < 0.0001) than the 7.0% (11 of 158) of placebo plus NBBM patients in whom ASDAS-MI was achieved. Of the placebo plus NBBM patients, 60.8% (96 of 158) switched to open-label treatment before week 52 compared to 12.6% (20 of 159) of the CZP plus NBBM patients.ConclusionAdding CZP to background medication is superior to adding placebo in patients with active nonradiographic axial SpA. These results indicate that remission in nonradiographic axial SpA treated without biologics occurs infrequently, demonstrating the need for treatment bey

ObjectiveAnti-tumor necrosis factor (anti-TNF) medications are effective in controlling chronic inflammatory diseases, but information about their use and safety in pregnancy is limited. Consequently, anti-TNF agents are often discontinued early in gestation. Certolizumab pegol (CZP), a PEGylated, Fc-free anti-TNF agent approved for the treatment of rheumatic diseases and/or Crohn's disease, has minimal to no active placental transfer. This analysis was undertaken to evaluate pregnancy outcomes in women receiving CZP, especially those exposed during early pregnancy.MethodsProspective and retrospective data on maternal CZP exposure were extracted from the UCB Pharma safety database through March 6, 2017. Analysis was limited to prospective reports to avoid potential bias associated with retrospective submissions. The numbers of live births, miscarriages, elective abortions, stillbirths, and major congenital malformations were ascertained.ResultsOf 1,137 prospectively reported pregnancies with maternal exposure to CZP, 528 (including 10 twin pregnancies) had 538 known outcomes: 459 live births (85.3%), 47 miscarriages (8.7%), 27 elective abortions (5.0%), and 5 stillbirths (0.9%). There were 8 major congenital malformations (1.7%) among the 459 infants. First trimester exposure occurred in 367 (81.2%) of 452 pregnancies resulting in 459 live births. Exposure during all 3 trimesters occurred in 201 (44.5%) of 452 pregnancies.ConclusionThis analysis represents the largest cohort of pregnant women exposed to an anti-TNF agent for management of chronic inflammatory diseases. Analysis of pregnancy outcomes does not indicate a teratogenic effect of CZP, compared to the general population, nor an increased risk of fetal death. The data are reassuring for women of childbearing age considering treatment with CZP.

Aim: To describe the persistence of biologic disease modifying anti-rheumatic drugs (bDMARDs) in Australian rheumatoid arthritis (RA) patients, and assess the influence of methotrexate and other conventional DMARD (cDMARD) concomitant medications, and treatment line on bDMARD persistence and glucocorticoids usage. Method(s): RA patients, from the 10% Australian Medicare random sample, aged >=18 for whom bDMARDs were dispensed were included. Individual sub-cutaneous (SC) anti-tumor necrosis factor-alpha (anti-TNFalpha) agents were combined as they were equivalent. Result(s): Data from 1230 patients were analyzed. For all patients the 12-month persistence rates (based on Kaplan-Meier estimates) were 76% for intravenous (IV) tocilizumab, 63% abatacept (SC/IV), 61% SC-anti-TNFs and 36% IV-infliximab. Persistence rates on first-line bDMARDs were 79% (tocilizumab and abatacept), 64% (SC-anti-TNFs) and 13% (infliximab); rates were sustained for tocilizumab but dropped to 49% for abatacept and 51% for SC-anti-TNFs in the second-line setting. Median treatment persistence was 40 months tocilizumab (95% CI: 30-ND), 33 months abatacept (95% CI: 20-ND); 22 months SC-anti-TNF (95% Cl: 18-27), and 4 months infliximab (95% CI: 2-13). Longer persistence was observed for SC-anti-TNFs and abatacept combined with methotrexate or other cDMARDs. For tocilizumab, persistence was robust with or without concomitant medications. The median oral glucocorticoid doses decreased from 4.1 mg/day (min 0, max 21) to 2.0 mg/day (min 0, max 17.3) over 2 years. Conclusion(s): Treatment persistence was longer on tocilizumab followed by abatacept then SC-anti-TNF therapy and was influenced by co-therapy. Glucocorticoid dosage decreased with bDMARD use. This real-world data highlights that persistence on bDMARDs differs according to biologics mode of action and co-therapy.Copyright © 2017 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd

Aim: To describe the persistence of biologic disease modifying anti-rheumatic drugs (bDMARDs) in Australian rheumatoid arthritis (RA) patients, and assess the influence of methotrexate and other conventional DMARD (cDMARD) concomitant medications, and treatment line on bDMARD persistence and glucocorticoids usage. Method(s): RA patients, from the 10% Australian Medicare random sample, aged >=18 for whom bDMARDs were dispensed were included. Individual sub-cutaneous (SC) anti-tumor necrosis factor-alpha (anti-TNFalpha) agents were combined as they were equivalent. Result(s): Data from 1230 patients were analyzed. For all patients the 12-month persistence rates (based on Kaplan-Meier estimates) were 76% for intravenous (IV) tocilizumab, 63% abatacept (SC/IV), 61% SC-anti-TNFs and 36% IV-infliximab. Persistence rates on first-line bDMARDs were 79% (tocilizumab and abatacept), 64% (SC-anti-TNFs) and 13% (infliximab); rates were sustained for tocilizumab but dropped to 49% for abatacept and 51% for SC-anti-TNFs in the second-line setting. Median treatment persistence was 40 months tocilizumab (95% CI: 30-ND), 33 months abatacept (95% CI: 20-ND); 22 months SC-anti-TNF (95% Cl: 18-27), and 4 months infliximab (95% CI: 2-13). Longer persistence was observed for SC-anti-TNFs and abatacept combined with methotrexate or other cDMARDs. For tocilizumab, persistence was robust with or without concomitant medications. The median oral glucocorticoid doses decreased from 4.1 mg/day (min 0, max 21) to 2.0 mg/day (min 0, max 17.3) over 2 years. Conclusion(s): Treatment persistence was longer on tocilizumab followed by abatacept then SC-anti-TNF therapy and was influenced by co-therapy. Glucocorticoid dosage decreased with bDMARD use. This real-world data highlights that persistence on bDMARDs differs according to biologics mode of action and co-therapy.Copyright © 2017 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd

[Abstract] Objectives: To assess the effectiveness and safety of certolizumab pegol (CZP) in Spanish patients with RA. Materials and methods: 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. Results: 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. Conclusions: 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., [Resumen] Objetivos: Evaluar la eficacia y la seguridad de certolizumab pegol (CZP) en pacientes españoles con artritis reumatoide (AR). Materiales y métodos: SONAR (NCT01526434), un estudio multicéntrico, observacional, prospectivo, abierto de 12 semanas. Pacientes con AR activa ≥3 meses, según criterios ACR, recibieron CZP (400 mg en las semanas 0, 2 y 4, seguido de 200 mg cada 2 semanas). La variable principal de eficacia fue el cambio desde el inicio (CDI) en el HAQ en la semana 12. Otras evaluaciones incluían el DAS28-VSG, la valoración del dolor (PtAAP-VAS) y el componente físico (PCS) y mental (MCS) del SF-36. La inflamación articular se estudió utilizando ecografía con Power Doppler (PDUS) midiendo derrame, hipertrofia sinovial y señal PD sinovial. Los resultados de PDUS evaluaron el CDI hasta la semana 12 en índices de hipertrofia sinovial, derrame y PD. Resultados: Un total de 77/80 pacientes recibieron ≥una dosis de CZP. La reducción media en 12 semanas desde el inicio (DE) fue de −0,6 (0,6) para HAQ y de −2,2 (1,5) para DAS28-VSG. La PtAAP-VAS disminuyó desde el inicio (media [DE]: −36,8 [26,8]) y hubo mejorías en los componentes PCS y MCS del SF-36. Los índices de señales de hipertrofia sinovial, derrame y PD disminuyeron desde el inicio hasta la semana 12. Se notificó una muerte durante el estudio. Conclusiones: Los pacientes españoles con AR mostraron mejoras en resultados clínicos, PDUS y notificados por el paciente durante 12 semanas de tratamiento con CZP. No hubo nuevas señales de seguridad, y el perfil de seguridad estaba en línea con estudios previos. Estos resultados respaldan los hallazgos de ensayos clínicos previos de CZP en AR.

ObjectiveAnti-tumor necrosis factor (anti-TNF) medications are effective in controlling chronic inflammatory diseases, but information about their use and safety in pregnancy is limited. Consequently, anti-TNF agents are often discontinued early in gestation. Certolizumab pegol (CZP), a PEGylated, Fc-free anti-TNF agent approved for the treatment of rheumatic diseases and/or Crohn's disease, has minimal to no active placental transfer. This analysis was undertaken to evaluate pregnancy outcomes in women receiving CZP, especially those exposed during early pregnancy.MethodsProspective and retrospective data on maternal CZP exposure were extracted from the UCB Pharma safety database through March 6, 2017. Analysis was limited to prospective reports to avoid potential bias associated with retrospective submissions. The numbers of live births, miscarriages, elective abortions, stillbirths, and major congenital malformations were ascertained.ResultsOf 1,137 prospectively reported pregnancies with maternal exposure to CZP, 528 (including 10 twin pregnancies) had 538 known outcomes: 459 live births (85.3%), 47 miscarriages (8.7%), 27 elective abortions (5.0%), and 5 stillbirths (0.9%). There were 8 major congenital malformations (1.7%) among the 459 infants. First trimester exposure occurred in 367 (81.2%) of 452 pregnancies resulting in 459 live births. Exposure during all 3 trimesters occurred in 201 (44.5%) of 452 pregnancies.ConclusionThis analysis represents the largest cohort of pregnant women exposed to an anti-TNF agent for management of chronic inflammatory diseases. Analysis of pregnancy outcomes does not indicate a teratogenic effect of CZP, compared to the general population, nor an increased risk of fetal death. The data are reassuring for women of childbearing age considering treatment with CZP.

Objectives.: To determine possible differences in serious adverse effects among the 10 currently approved biological and targeted synthetic DMARDs (b/ts-DMARDs) for RA.Methods.: Systematic review in bibliographic databases, trial registries and websites of regulatory agencies identified randomized trials of approved b/ts-DMARDs for RA. Network meta-analyses using mixed-effects Poisson regression models were conducted to calculate rate ratios for serious adverse events (SAEs) and deaths between each of the 10 drugs and control (i.e. no b/ts-DMARD treatment), based on subjects experiencing an event in relation to person-years. Confidence in the estimates was assessed by applying the Grading of Recommendations Assessment, Development and Evaluation approach (GRADE).Results.: A total of 117 trials (47 615 patients) were included. SAEs were more common with certolizumab compared with abatacept (rate ratio = 1.58, 95% CI: 1.18, 2.14), adalimumab (1.36, 95% CI: 1.02, 1.81), etanercept (1.60, 95% CI: 1.18, 2.17), golimumab (1.45, 95% CI: 1.00, 2.08), rituximab (1.63, 95% CI: 1.16, 2.30), tofacitinib (1.44, 95% CI: 1.03, 2.02) and control (1.45, 95% CI: 1.13, 1.87); and tocilizumab compared with abatacept (1.30, 95% CI: 1.03, 1.65), etanercept (1.31, 95% CI: 1.04, 1.67) and rituximab (1.34, 95% CI: 1.01, 1.78). No other comparisons were statistically significant. Accounting for study duration confirmed our findings for up to 6 months' treatment but not for longer-term treatment (6-24 months). No differences in mortality between b/ts-DMARDs and control were found. Based on the GRADE approach, confidence in the estimates was low due to lack of head-to-head comparison trials and imprecision in indirect estimates.Conclusion.: Despite low confidence in the estimates, our analysis found potential differences in rates of SAEs. Our data suggest caution should be taken when deciding among available drugs.Systematic review registration number.: PROSPERO

Aim: To investigate the usage of concomitant glucocorticoids (GC) with biologic (b) DMARD for the treatment of rheumatoid arthritis (RA) patients. Method(s): Concessional (government subsidised) RA patients >=18 years old for whom bDMARD were first dispensed for their RA (01 August, 2010 to 31 July 2013), and who were in the Australian Medicare 10% sample database, provided by the Department of Health and Aging, were followed for 2 years. bDMARD included: abatacept (IV+SC), adalimumab, certolizumab pegol, etanercept, golimumab, infliximab and tocilizumab. Data were analysed using descriptive statistics for continuous variables and frequency counts for categorical variables. Individual anti-TNF were equivalent in all analyses and therefore were combined for simplicity. Result(s): Data from 269 patients were analysed. Of the patients who received oral GC at some point during the study period (86%; n = 230), 49% were >=65 years old and 51% were 18-64 years old. The majority (81%) were females. For all patients (n = 230), the median dose of oral GC was 4.1 mg/day (minimum: 0 mg/day, maximum: 21 mg/day) at 1- year prior bDMARD initiation, 2.9 mg/day (minimum: 0 mg/day, maximum: 22.2 mg/day) and 2.0 mg/day (minimum: 0 mg/day, maximum: 17.3 mg/day) at 1-2 years respectively, post-bDMARD initiation. Daily dose changes at 1-2 years post-initiation of bDMARD from 1-year before initiation were significant for all bDMARD (P < 0.0001), all anti-TNF (P < 0.0001) and tocilizumab (P = 0.0002). The percentage of patients who stopped GC at any time post-initiation of bDMARD was 43% for all RA bDMARD, 44% for all anti-TNF, 27% for abatacept and 39% for tocilizumab. Thirty-one percent of patients who remained on biologics during the observation period in the 'all RA bDMARDs' group increased GC dose and 60% decreased after 1-year. Conclusion(s): In the Australian setting, the majority of RA patients who were taking oral glucocorticoids had reductions in their daily doses after initiatio

Aim: To investigate the persistence on biologic (b) DMARDS in the Australian landscape and identify factors that might influence biologic survival in rheumatoid arthritis (RA) patients. Method(s): RA patients aged >=18 for whom biologics were dispensed for their RA and who were in the Australian Medicare 10% sample database (dating from 01-August 2010 to 31-June 2014) provided by the Department of Health and Aging through an Australian healthcare consulting company were included. bDMARDS included: abatacept (ABA), adalimumab, certolizumab pegol, etanercept, golimumab, infliximab (INF) and tocilizumab (TCZ). Data were analysed using descriptive statistics for continuous variables and frequency counts for categorical variables. Time-to-endpoints were summarised using Kaplan-Meier (K-M) methodology. Individual subcutaneous (SC) anti-TNFs were equivalent in all analyses and therefore were combined for simplicity. Result(s): Data from 1230 patients were analysed; 27% were >= 65 years old and 73% were between 18-64 years old. The majority (73%) were females. For all patients, the percentage (based on K-M estimates) who continued on treatment (combination and monotherapy) at 6-months (mo) after commencement was 87%-TCZ, 78%-ABA, 72%-SC anti-TNFs and 40%- INF. At 6-months, 86%-TCZ of patients, 85%-ABA and 64%-Sc anti- TNFs continued treatment as first-line; and 91%-TCZ, 73%-ABA and 63% Sc anti-TNFs continued as second-line. Median time-to-stopping treatment was 40 mo-TCZ (95% CI:30-ND), 33 mo-ABA (95% CI:20- ND); 22 mo-SC anti-TNF (95% Cl:18-27), and 4 mo-for INF (95% CI:2- 13). Longer median treatment persistence was observed for concomitant SC anti-TNFs (27 mo vs 14 mo; p < 0.0001) and ABA (although not statistically significant, 33 mo versus 23 mo; p = 0.26) with MTX or other DMARDs than for monotherapy (but not TCZ). Age had no effect on persistence. Conclusion(s): Treatment persistence was longer onTCZ followed by ABA then SC anti-TNFs therapy. This real-world data hel

Aim: To investigate the usage of concomitant glucocorticoids (GC) with biologic (b) DMARD for the treatment of rheumatoid arthritis (RA) patients. Method(s): Concessional (government subsidised) RA patients >=18 years old for whom bDMARD were first dispensed for their RA (01 August, 2010 to 31 July 2013), and who were in the Australian Medicare 10% sample database, provided by the Department of Health and Aging, were followed for 2 years. bDMARD included: abatacept (IV+SC), adalimumab, certolizumab pegol, etanercept, golimumab, infliximab and tocilizumab. Data were analysed using descriptive statistics for continuous variables and frequency counts for categorical variables. Individual anti-TNF were equivalent in all analyses and therefore were combined for simplicity. Result(s): Data from 269 patients were analysed. Of the patients who received oral GC at some point during the study period (86%; n = 230), 49% were >=65 years old and 51% were 18-64 years old. The majority (81%) were females. For all patients (n = 230), the median dose of oral GC was 4.1 mg/day (minimum: 0 mg/day, maximum: 21 mg/day) at 1- year prior bDMARD initiation, 2.9 mg/day (minimum: 0 mg/day, maximum: 22.2 mg/day) and 2.0 mg/day (minimum: 0 mg/day, maximum: 17.3 mg/day) at 1-2 years respectively, post-bDMARD initiation. Daily dose changes at 1-2 years post-initiation of bDMARD from 1-year before initiation were significant for all bDMARD (P < 0.0001), all anti-TNF (P < 0.0001) and tocilizumab (P = 0.0002). The percentage of patients who stopped GC at any time post-initiation of bDMARD was 43% for all RA bDMARD, 44% for all anti-TNF, 27% for abatacept and 39% for tocilizumab. Thirty-one percent of patients who remained on biologics during the observation period in the 'all RA bDMARDs' group increased GC dose and 60% decreased after 1-year. Conclusion(s): In the Australian setting, the majority of RA patients who were taking oral glucocorticoids had reductions in their daily doses after initiatio

Aim: To investigate the persistence on biologic (b) DMARDS in the Australian landscape and identify factors that might influence biologic survival in rheumatoid arthritis (RA) patients. Method(s): RA patients aged >=18 for whom biologics were dispensed for their RA and who were in the Australian Medicare 10% sample database (dating from 01-August 2010 to 31-June 2014) provided by the Department of Health and Aging through an Australian healthcare consulting company were included. bDMARDS included: abatacept (ABA), adalimumab, certolizumab pegol, etanercept, golimumab, infliximab (INF) and tocilizumab (TCZ). Data were analysed using descriptive statistics for continuous variables and frequency counts for categorical variables. Time-to-endpoints were summarised using Kaplan-Meier (K-M) methodology. Individual subcutaneous (SC) anti-TNFs were equivalent in all analyses and therefore were combined for simplicity. Result(s): Data from 1230 patients were analysed; 27% were >= 65 years old and 73% were between 18-64 years old. The majority (73%) were females. For all patients, the percentage (based on K-M estimates) who continued on treatment (combination and monotherapy) at 6-months (mo) after commencement was 87%-TCZ, 78%-ABA, 72%-SC anti-TNFs and 40%- INF. At 6-months, 86%-TCZ of patients, 85%-ABA and 64%-Sc anti- TNFs continued treatment as first-line; and 91%-TCZ, 73%-ABA and 63% Sc anti-TNFs continued as second-line. Median time-to-stopping treatment was 40 mo-TCZ (95% CI:30-ND), 33 mo-ABA (95% CI:20- ND); 22 mo-SC anti-TNF (95% Cl:18-27), and 4 mo-for INF (95% CI:2- 13). Longer median treatment persistence was observed for concomitant SC anti-TNFs (27 mo vs 14 mo; p < 0.0001) and ABA (although not statistically significant, 33 mo versus 23 mo; p = 0.26) with MTX or other DMARDs than for monotherapy (but not TCZ). Age had no effect on persistence. Conclusion(s): Treatment persistence was longer onTCZ followed by ABA then SC anti-TNFs therapy. This real-world data hel

Objectives: To compare the efficacy and safety of certolizumab pegol (CZP) with and without loading dose (LD) in a post-hoc analysis of two Japanese clinical studies. Methods: Data from the double-blind trials (DBT) J-RAPID and HIKARI, and their open-label extension (OLE) studies, were used. Patients randomized to CZP 200 mg every 2 weeks (Q2W) groups starting with LD (400 mg Weeks 0/2/4; LD group; J-RAPID: n = 82, HIKARI: n = 116) and patients randomized to placebo groups who subsequently started CZP Q2W without LD in the OLEs (No-LD group; J-RAPID: n = 61, HIKARI: n = 99) were analyzed. Efficacy and pharmacokinetics were assessed during 24 weeks. Adverse events were reported from all studies. Results: In both trials, the LD groups showed more rapid initial ACR20/50/70 kinetics, and maintained higher ACR50/70 responses until 24 weeks, compared with the No-LD groups. Anti-CZP antibody development was less frequent in the LD groups (J-RAPID: 1.2% versus 4.9%; HIKARI: 17.2% versus 27.3%). Similar safety profiles were reported between LD and No-LD groups (any AEs: 281.8 versus 315.7 [J-RAPID], 282.6 versus 321.3 [HIKARI] [incidence rate/100 patient-years]). Conclusions: Despite limitations, including comparing DBT and OLE studies, these results suggest that a CZP LD improves clinical response in active rheumatoid arthritis without altering the safety profile.

Objectives: To compare the efficacy and safety of certolizumab pegol (CZP) with and without loading dose (LD) in a post-hoc analysis of two Japanese clinical studies. Methods: Data from the double-blind trials (DBT) J-RAPID and HIKARI, and their open-label extension (OLE) studies, were used. Patients randomized to CZP 200 mg every 2 weeks (Q2W) groups starting with LD (400 mg Weeks 0/2/4; LD group; J-RAPID: n = 82, HIKARI: n = 116) and patients randomized to placebo groups who subsequently started CZP Q2W without LD in the OLEs (No-LD group; J-RAPID: n = 61, HIKARI: n = 99) were analyzed. Efficacy and pharmacokinetics were assessed during 24 weeks. Adverse events were reported from all studies. Results: In both trials, the LD groups showed more rapid initial ACR20/50/70 kinetics, and maintained higher ACR50/70 responses until 24 weeks, compared with the No-LD groups. Anti-CZP antibody development was less frequent in the LD groups (J-RAPID: 1.2% versus 4.9%; HIKARI: 17.2% versus 27.3%). Similar safety profiles were reported between LD and No-LD groups (any AEs: 281.8 versus 315.7 [J-RAPID], 282.6 versus 321.3 [HIKARI] [incidence rate/100 patient-years]). Conclusions: Despite limitations, including comparing DBT and OLE studies, these results suggest that a CZP LD improves clinical response in active rheumatoid arthritis without altering the safety profile.

Background: Current guidelines for rheumatoid arthritis (RA) recommend starting a biologic DMARD in combination with methotrexate (MTX) in patients responding insufficiently to MTX and/or other synthetic disease modifying anti-rheumatic drugs (DMARDs) with or without glucocorticoids. There is limited data on drug survival studying all modes of action in the same population. Objective(s): The primary objective was to describe the persistence on biologic (b) DMARDS in the Australian landscape. The secondary objectives were to investigate the influence of MTX and other DMARD concomitant medications, effect of patient age at initiation and bDMARD treatment line on biologic persistence. Method(s): RA patients aged >=18 for whom biologics were dispensed for their RA and who were in the Australian Medicare 10% sample database (dating from 01 August 2010 to 31 June 2014) provided by the Department of Health and Aging through an Australian healthcare consulting company (PROSPECTION) were included in the study. The following bDMARDS were included abatacept (ABA), adalimumab, certolizumab pegol, etanercept, golimumab, infliximab (INF) and tocilizumab (TCZ). The duration of treatment was determined for each treatment regimen. Data were analysed using descriptive statistics for continuous variables and frequency counts for categorical variables. Time-to endpoints was summarised using Kaplan-Meier (K-M) methodology. Individual sub-cutaneous (SC) anti-TNFs were equivalent in all analyses and therefore were combined for simplicity. Result(s): Data from 1230 patients were included in the analysis; 27% were >=65 years old and 73% were between 18-64 years old. The majority (73%) were females. For all patients, the percentage (based on K-M estimates) who continued on treatment at 6 months (mo) after commencement was 84% for TCZ, 75% for ABA, 69% for SC anti-TNFs and 40% for INF. Median time to stopping treatment was 39 mo (95% CI:29-ND) for TCZ, 32 mo (95% CI:19-ND) for ABA; 21 mo (95%

Background: Current guidelines for rheumatoid arthritis (RA) recommend starting a biologic DMARD in combination with methotrexate (MTX) in patients responding insufficiently to MTX and/or other synthetic disease modifying anti-rheumatic drugs (DMARDs) with or without glucocorticoids. There is limited data on drug survival studying all modes of action in the same population. Objective(s): The primary objective was to describe the persistence on biologic (b) DMARDS in the Australian landscape. The secondary objectives were to investigate the influence of MTX and other DMARD concomitant medications, effect of patient age at initiation and bDMARD treatment line on biologic persistence. Method(s): RA patients aged >=18 for whom biologics were dispensed for their RA and who were in the Australian Medicare 10% sample database (dating from 01 August 2010 to 31 June 2014) provided by the Department of Health and Aging through an Australian healthcare consulting company (PROSPECTION) were included in the study. The following bDMARDS were included abatacept (ABA), adalimumab, certolizumab pegol, etanercept, golimumab, infliximab (INF) and tocilizumab (TCZ). The duration of treatment was determined for each treatment regimen. Data were analysed using descriptive statistics for continuous variables and frequency counts for categorical variables. Time-to endpoints was summarised using Kaplan-Meier (K-M) methodology. Individual sub-cutaneous (SC) anti-TNFs were equivalent in all analyses and therefore were combined for simplicity. Result(s): Data from 1230 patients were included in the analysis; 27% were >=65 years old and 73% were between 18-64 years old. The majority (73%) were females. For all patients, the percentage (based on K-M estimates) who continued on treatment at 6 months (mo) after commencement was 84% for TCZ, 75% for ABA, 69% for SC anti-TNFs and 40% for INF. Median time to stopping treatment was 39 mo (95% CI:29-ND) for TCZ, 32 mo (95% CI:19-ND) for ABA; 21 mo (95%

Background: The regional availability of specialized physicians is an important aspect in healthcare of patients with IBD. The association between physician density and healthcare is not yet clear. Most studies did not consider district type, which reflects population density. Our research question was, “Do specialist density and district type influence the healthcare of IBD patients in Germany?” Methods: We combined a claims dataset from a German health insurance fund with population and physician data. Four main aspects were investigated: regular specialist visits, drug therapies, surveillance colonoscopy, and IBD-related hospitalizations. Various regression analyses were performed. Results: The study cohort was comprised of 21,771 individuals, including 9282 patients with Crohn disease and 12,489 patients with ulcerative colitis. Patients who were living in districts with higher specialist densities were more likely to attend specialist visits on a regular basis. No difference in the frequencies of TNF-alpha inhibitor therapies was found. However, individuals from urban areas were more likely to receive a permanent immunosuppressive therapy with continuous specialist support. Conclusions: The results revealed that some aspects had positive effects on the probability of implementing healthcare in accordance with pathways and guidelines. No clear evidence of a general healthcare undersupply in rural areas was found.

IntroductionAs patients with rheumatoid arthritis (RA) receive treatment with anti-tumour necrosis factors over several years, it is important to evaluate their long-term safety and efficacy. The objective of this study was to examine the safety and benefits of certolizumab pegol (CZP)+methotrexate (MTX) treatment for almost 5 years in patients with RA.MethodsPatients who completed the 24-week Rheumatoid Arthritis Prevention of Structural Damage (RAPID) 2 randomized controlled trial (RCT; NCT00160602), or who were American College of Rheumatology (ACR) 20 non-responders at Week 16, entered the open-label extension (OLE; NCT00160641). After ≥6 months treatment with CZP 400 mg every two weeks (Q2W), dose was reduced to 200 mg Q2W, the approved maintenance dose. Safety data are presented from all patients who received ≥1 dose CZP (Safety population, n=612). Efficacy data are presented to Week 232 for the intent-to-treat (ITT, n=492) and Week 24 CZP RCT Completer (n=342) populations, and through 192 weeks of dose-reduction for the Dose-reduction population (patients whose CZP dose was reduced to 200 mg, n=369). Radiographic progression (modified total Sharp score change from RCT baseline >0.5) to Week 128 is reported for the Week 24 CZP Completers.ResultsIn the RCT, 619 patients were randomized to CZP+MTX (n=492) or placebo+MTX (n=127). Overall, 567 patients (91.6%) entered the OLE: 447 CZP and 120 placebo patients. Of all randomized patients, 358 (57.8%) were ongoing at Week 232. Annual drop-out rates during the first four years ranged from 8.4-15.0%. Event rates per 100 patient-years were 163.0 for adverse events (AEs) and 15.7 for serious AEs. Nineteen patients (3.1%) had fatal AEs (incidence rate=0.8). Clinical improvements in the RCT were maintained to Week 232 in the CZP Completers: mean Disease Activity Score 28 (Erythrocyte Sedimentation Rate) change from baseline was -3.4 and ACR20/50/70 responses 68.4%/47.1%/25.1% (non-responder imputation). Similar improve

OBJECTIVES: To identify the first time point of an MRI-verified response to certolizumab pegol (CZP) therapy in patients with rheumatoid arthritis (RA).METHODS: Forty-one patients with active RA despite disease-modifying antirheumatic drug therapy were randomised 2:1 to CZP (CZP loading dose 400 mg every 2 weeks at weeks 0-4; CZP 200 mg every 2 weeks at weeks 6-16) or placebo→CZP (placebo at weeks 0-2; CZP loading dose at weeks 2-6; CZP 200 mg every 2 weeks at weeks 8-16). Contrast-enhanced MRI of one hand and wrist was acquired at baseline (week 0) and weeks 1, 2, 4, 8 and 16. All six time points were read simultaneously, blinded to time, using the Outcome Measures in Rheumatology Clinical Trials RA MRI scoring system. Primary outcome was change in synovitis score in the CZP group; secondary outcomes were change in bone oedema (osteitis) and erosion scores and clinical outcome measures.RESULTS: Forty patients were treated (27 CZP, 13 placebo→CZP), and 36 (24 CZP, 12 placebo→CZP) completed week 16. In the CZP group, there were significant reductions from baseline synovitis (Hodges-Lehmann estimate of median change, -1.5, p=0.049) and osteitis scores (-2.5, p=0.031) at week 16. Numerical, but statistically insignificant, MRI inflammation reductions were observed at weeks 1-2 in the CZP group. No significant change was seen in bone erosion score. Improvements across all clinical outcomes were seen in the CZP group.CONCLUSIONS: CZP reduced MRI synovitis and osteitis scores at week 16, despite small sample size and the technical challenge of reading six time points simultaneously. This study provides essential information on optimal MRI timing for subsequent trials.TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, NCT01235598.

Aims: To investigate the persistence on biologic (b) DMARDS in the Australian landscape and identify factors that might influence biologic survival in rheumatoid arthritis (RA) patients. Method(s): RA patients aged >=18 for whom biologics were dispensed for their RA and who were in the Australian Medicare 10% sample database (dating from 01-August 2010 to 31-June 2014) provided by the Department of Health and Aging through an Australian healthcare consulting company were included. bDMARDS included: abatacept (ABA), adalimumab, certolizumab pegol, etanercept, golimumab, infliximab (INF) and tocilizumab (TCZ). Data were analysed using descriptive statistics for continuous variables and frequency counts for categorical variables. Time-to-endpoints were summarised using Kaplan-Meier (K-M) methodology. Individual sub-cutaneous (SC) anti-TNFs were equivalent in all analyses and therefore were combined for simplicity. Result(s): Data from 1230 patients were analysed; 27% were >=65 years old and 73% were between 18-64 years old. The majority (73%) were females. For all patients, the percentage (based on K-M estimates) who continued on treatment (combination and monotherapy) at 6- months (mo) after commencement was 87%-TCZ, 78%-ABA, 72%-SC anti-TNFs and 40%-INF. At 6-months, 86%-TCZ of patients, 85%-ABA and 64%-Sc anti-TNFs continued treatment as first-line; and 91%-TCZ, 73%-ABA and 63% Sc anti-TNFs continued as second-line. Median time-to-stopping treatment was 40mo-TCZ (95% CI: 30-ND), 33mo-ABA (95% CI: 20-ND); 22mo-SC anti-TNF (95% Cl: 18-27), and 4mo-for INF (95% CI: 2-13). Longer median treatment persistence was observed for concomitant SC anti-TNFs (27mo versus 14mo; P < 0.0001) and ABA (although not statistically significant, 33mo versus 23mo; P = 0.26) with MTX or other DMARDs than for monotherapy (but not TCZ). Age had no effect on persistence. Conclusion(s): Treatment persistence was longer on TCZ followed by ABA then SC anti-TNFs therapy. This real-world data help

Aims: To investigate the persistence on biologic (b) DMARDS in the Australian landscape and identify factors that might influence biologic survival in rheumatoid arthritis (RA) patients. Method(s): RA patients aged >=18 for whom biologics were dispensed for their RA and who were in the Australian Medicare 10% sample database (dating from 01-August 2010 to 31-June 2014) provided by the Department of Health and Aging through an Australian healthcare consulting company were included. bDMARDS included: abatacept (ABA), adalimumab, certolizumab pegol, etanercept, golimumab, infliximab (INF) and tocilizumab (TCZ). Data were analysed using descriptive statistics for continuous variables and frequency counts for categorical variables. Time-to-endpoints were summarised using Kaplan-Meier (K-M) methodology. Individual sub-cutaneous (SC) anti-TNFs were equivalent in all analyses and therefore were combined for simplicity. Result(s): Data from 1230 patients were analysed; 27% were >=65 years old and 73% were between 18-64 years old. The majority (73%) were females. For all patients, the percentage (based on K-M estimates) who continued on treatment (combination and monotherapy) at 6- months (mo) after commencement was 87%-TCZ, 78%-ABA, 72%-SC anti-TNFs and 40%-INF. At 6-months, 86%-TCZ of patients, 85%-ABA and 64%-Sc anti-TNFs continued treatment as first-line; and 91%-TCZ, 73%-ABA and 63% Sc anti-TNFs continued as second-line. Median time-to-stopping treatment was 40mo-TCZ (95% CI: 30-ND), 33mo-ABA (95% CI: 20-ND); 22mo-SC anti-TNF (95% Cl: 18-27), and 4mo-for INF (95% CI: 2-13). Longer median treatment persistence was observed for concomitant SC anti-TNFs (27mo versus 14mo; P < 0.0001) and ABA (although not statistically significant, 33mo versus 23mo; P = 0.26) with MTX or other DMARDs than for monotherapy (but not TCZ). Age had no effect on persistence. Conclusion(s): Treatment persistence was longer on TCZ followed by ABA then SC anti-TNFs therapy. This real-world data help

Biologic therapies have revolutionized the treatment of rheumatoid arthritis, a common chronic inflammatory disease, mainly characterized by the chronic inflammation of the joints. The activity and progression of the disease are highly variable, both between subjects and between the successive assessments for the same subject. Standardized assessments of clinical variables have been developed to reflect the disease activity and evaluate new therapies. Pharmacokinetics-pharmacodynamic (PKPD) models and methods for analyzing the generated time-course data are needed to improve the interpretation of the clinical trials’ outcomes, and to describe the variability between subjects, including patients characteristics, disease factors and the use of concomitant treatments that may affect the response to treatment. In addition, good simulation properties are also desirable for predicting clinical responses for various populations or for different dosing schedules. The aim of this thesis was to develop methods and models for analyzing pharmacokinetic and pharmacokinetic-pharmacodynamic (PKPD) data from rheumatoid arthritis patients, illustrated by treatment with a new anti-TNFα biologic drug under clinical development, certolizumab pegol. Two models were developed that characterized the relationship between the exposure to the drug and the efficacy ACR variables that represent improvement of the disease; a logistic-type Markov model for 20% improvement (ACR20) and a continuous-type Markov model for simultaneous analysis of 20% (ACR20), 50% (ACR50) and 70% (ACR70) improvement. Both models accounted for the within-subjects correlation in the successive clinical assessments and were able to capture the observed ACR responses over time. Simulations from these models of the ACR20 response rate supported dosing regimens of 400 mg at weeks 0, 2 and 4 to achieve a rapid onset of response to the treatment, followed by 200 mg every 2 weeks, or alternative maintenance regimen of 400 mg

This 52-week, randomised, double-blind phase IIIb study assessed efficacy and safety of certolizumab pegol (CZP) as add-on therapy to non-biologic disease-modifying antirheumatic drugs (DMARDs) in rheumatoid arthritis (RA) patients with low to moderate disease activity, and stopping therapy in patients in sustained remission.

IntroductionAs patients with rheumatoid arthritis (RA) receive treatment with anti-tumour necrosis factors over several years, it is important to evaluate their long-term safety and efficacy. The objective of this study was to examine the safety and benefits of certolizumab pegol (CZP)+methotrexate (MTX) treatment for almost 5 years in patients with RA.MethodsPatients who completed the 24-week Rheumatoid Arthritis Prevention of Structural Damage (RAPID) 2 randomized controlled trial (RCT; NCT00160602), or who were American College of Rheumatology (ACR) 20 non-responders at Week 16, entered the open-label extension (OLE; NCT00160641). After ≥6 months treatment with CZP 400 mg every two weeks (Q2W), dose was reduced to 200 mg Q2W, the approved maintenance dose. Safety data are presented from all patients who received ≥1 dose CZP (Safety population, n=612). Efficacy data are presented to Week 232 for the intent-to-treat (ITT, n=492) and Week 24 CZP RCT Completer (n=342) populations, and through 192 weeks of dose-reduction for the Dose-reduction population (patients whose CZP dose was reduced to 200 mg, n=369). Radiographic progression (modified total Sharp score change from RCT baseline >0.5) to Week 128 is reported for the Week 24 CZP Completers.ResultsIn the RCT, 619 patients were randomized to CZP+MTX (n=492) or placebo+MTX (n=127). Overall, 567 patients (91.6%) entered the OLE: 447 CZP and 120 placebo patients. Of all randomized patients, 358 (57.8%) were ongoing at Week 232. Annual drop-out rates during the first four years ranged from 8.4-15.0%. Event rates per 100 patient-years were 163.0 for adverse events (AEs) and 15.7 for serious AEs. Nineteen patients (3.1%) had fatal AEs (incidence rate=0.8). Clinical improvements in the RCT were maintained to Week 232 in the CZP Completers: mean Disease Activity Score 28 (Erythrocyte Sedimentation Rate) change from baseline was -3.4 and ACR20/50/70 responses 68.4%/47.1%/25.1% (non-responder imputation). Similar improve

Objective. This 24-week, placebo-controlled, double-blind, randomized study (NCT00791921) investigated efficacy and safety of certolizumab pegol (CZP) in Japanese rheumatoid arthritis (RA) patients in whom methotrexate (MTX) cannot be administered. Methods. A total of 230 patients were randomized to subcutaneous CZP 200 mg (induction dosing: 400 mg at Weeks 0, 2 and 4) or placebo every 2 weeks. Results. ACR20 responses with CZP were rapid and significant versus placebo at Week 1, sustained to Week 12 (67.2% vs. 14.9%) and Week 24 (63.8% vs. 11.4%). Week 24-modified Total Sharp Score (mTSS) change from baseline (CFB) was 0.48 (CZP) versus 2.45 (placebo). CZP treatment was associated with higher Week 12 ACR20 responses versus placebo (with non-MTX disease modifying antirheumatic drugs [DMARDs], 74.2% vs. 20.0%; without [monotherapy], 59.3% vs. 8.2%) and inhibition of radiographic progression at Week 24 (mTSS CFB; with non-MTX DMARDs, 0.24 vs. 1.61; monotherapy, 0.68 vs. 3.65). Incidences of serious adverse events were 11.2% (CZP) and 2.6% (placebo); one CZP patient died of dissecting aortic aneurysm. Conclusion. CZP treatment with and without non-MTX DMARDs in Japanese patients in whom MTX cannot be administered resulted in rapid, sustained reductions in RA signs and symptoms. Notably, CZP monotherapy showed significant inhibition of radiographic progression.

Objectives. This 24-week, multicenter, double-blind, randomized, placebo-controlled study (NCT00791999) compared efficacy and safety of certolizumab pegol (CZP) in combination with methotrexate (MTX) vs placebo plus MTX in Japanese rheumatoid arthritis (RA) patients with inadequate response to MTX. Methods. In total, 316 patients were randomized 1:1:1:1 to subcutaneous CZP 100, 200, or 400 mg (induction dose: 200 mg or 400 mg CZP at Weeks 0, 2, and 4) plus MTX or placebo plus MTX every 2 weeks. Primary endpoint was ACR20 response at Week 12. Results. ACR20 response rates were 62.5%, 76.8%, 77.6%, and 28.6% at Week 12, and 61.1%, 73.2%, 71.8%, and 24.7% at Week 24 for CZP 100, 200, and 400 mg, and placebo groups, respectively, with statistical significance between each CZP group and placebo. Change in Total Sharp Score over 24 weeks was significantly smaller in CZP 200 and 400 mg groups vs placebo. Improvements in health-related quality of life (HRQoL) were observed in all three CZP groups vs placebo. Incidence of adverse events was similar between CZP groups. Conclusions. CZP plus MTX resulted in rapid, sustained reductions in RA signs and symptoms in Japanese patients with inadequate response to MTX, with significant inhibition of radiographic progression and improved HRQoL.

Objectives. This 24-week, multicenter, double-blind, randomized, placebo-controlled study (NCT00791999) compared efficacy and safety of certolizumab pegol (CZP) in combination with methotrexate (MTX) vs placebo plus MTX in Japanese rheumatoid arthritis (RA) patients with inadequate response to MTX. Methods. In total, 316 patients were randomized 1:1:1:1 to subcutaneous CZP 100, 200, or 400 mg (induction dose: 200 mg or 400 mg CZP at Weeks 0, 2, and 4) plus MTX or placebo plus MTX every 2 weeks. Primary endpoint was ACR20 response at Week 12. Results. ACR20 response rates were 62.5%, 76.8%, 77.6%, and 28.6% at Week 12, and 61.1%, 73.2%, 71.8%, and 24.7% at Week 24 for CZP 100, 200, and 400 mg, and placebo groups, respectively, with statistical significance between each CZP group and placebo. Change in Total Sharp Score over 24 weeks was significantly smaller in CZP 200 and 400 mg groups vs placebo. Improvements in health-related quality of life (HRQoL) were observed in all three CZP groups vs placebo. Incidence of adverse events was similar between CZP groups. Conclusions. CZP plus MTX resulted in rapid, sustained reductions in RA signs and symptoms in Japanese patients with inadequate response to MTX, with significant inhibition of radiographic progression and improved HRQoL.

Objective. This 24-week, placebo-controlled, double-blind, randomized study (NCT00791921) investigated efficacy and safety of certolizumab pegol (CZP) in Japanese rheumatoid arthritis (RA) patients in whom methotrexate (MTX) cannot be administered. Methods. A total of 230 patients were randomized to subcutaneous CZP 200 mg (induction dosing: 400 mg at Weeks 0, 2 and 4) or placebo every 2 weeks. Results. ACR20 responses with CZP were rapid and significant versus placebo at Week 1, sustained to Week 12 (67.2% vs. 14.9%) and Week 24 (63.8% vs. 11.4%). Week 24-modified Total Sharp Score (mTSS) change from baseline (CFB) was 0.48 (CZP) versus 2.45 (placebo). CZP treatment was associated with higher Week 12 ACR20 responses versus placebo (with non-MTX disease modifying antirheumatic drugs [DMARDs], 74.2% vs. 20.0%; without [monotherapy], 59.3% vs. 8.2%) and inhibition of radiographic progression at Week 24 (mTSS CFB; with non-MTX DMARDs, 0.24 vs. 1.61; monotherapy, 0.68 vs. 3.65). Incidences of serious adverse events were 11.2% (CZP) and 2.6% (placebo); one CZP patient died of dissecting aortic aneurysm. Conclusion. CZP treatment with and without non-MTX DMARDs in Japanese patients in whom MTX cannot be administered resulted in rapid, sustained reductions in RA signs and symptoms. Notably, CZP monotherapy showed significant inhibition of radiographic progression.