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Objectives To assess the impact of baseline RF level on drug concentrations and efficacy of certolizumab pegol [CZP; TNF inhibitor (TNFi) without a crystallizable fragment (Fc)] and adalimumab (ADA; Fc-containing TNFi) in patients with RA. Methods The phase 4 EXXELERATE study (NCT01500278) was a 104-week, randomized, single-blind (double-blind until week 12; investigator-blind thereafter), head-to-head study of CZP vs ADA in patients with RA. In this post hoc analysis, we report drug concentration and efficacy outcomes stratified by baseline RF quartile (≤Q3 or >Q3). Results Baseline data by RF quartiles were available for 453 CZP-randomized and 454 ADA-randomized patients (≤Q3: ≤204 IU/ml; >Q3: >204 IU/ml). From week 12, the area under the curve (AUC) of ADA concentration was lower in patients with RF >204 IU/ml vs patients with RF ≤204 IU/ml; the AUC of CZP concentration was similar in patients with RF ≤204 IU/ml and >204 IU/ml. For patients with RF ≤204 IU/ml, disease activity score (DAS28)-CRP was similar between CZP- and ADA-treated patients through week 104. For patients with RF >204 IU/ml, mean DAS28-CRP was lower in CZP- vs ADA-treated patients at week 104. The proportion of patients with RF >204 IU/ml achieving DAS28-CRP low disease activity at week 104 was greater in CZP- vs ADA-treated patients. Conclusion CZP was associated with maintained drug concentration and efficacy in patients with RA and high RF and may therefore be a more suitable therapeutic option than TNFis with an Fc fragment in these patients. Trial registration Clinicaltrials.gov, http://clinicaltrials.gov , NCT01500278 [ABSTRACT FROM AUTHOR]

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

In pregnancy, a plethora of factors causes changes in maternal immunity. Uveitis flare-ups are more frequent in the first trimester and in undertreated patients. Management of non-infectious uveitis during pregnancy remains understudied. A bibliographic review to consolidate existing evidence was performed by a multidisciplinary group of Ophthalmologists, Gynaecologists and Rheumatologists. Our group recommends initial management with minimum-required doses of corticosteroids, preferably locally, to treat intraocular inflammation whilst ensuring good neonatal outcomes. If ineffective, clinicians should consider addition of Cyclosporine, Azathioprine or Certolizumab pegol, which are seemingly safe in pregnancy. Other therapies (such as Methotrexate, Mycophenolate Mofetil and alkylating agents) are teratogenic or have a detrimental effect on the foetus. Furthermore, careful multidisciplinary preconception discussions and close follow-up are recommended, monitoring for flare-ups and actively tapering medication doses, with a primary endpoint focused on protecting ocular tissues from inflammation, whilst giving minimal risk of poor pregnancy and foetal outcomes. [ABSTRACT FROM AUTHOR]

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Objective: While biologics have been used for the patients with psoriatic arthritis, there remains to be unknown concerning long-term retention rates. This study aims to present real-world data about long-term retention rates of biologics for the patients with psoriatic arthritis, and to undertake an analysis of the contributing factors. Methods: We examined retention rates and the reasons for discontinuation for biologics (adalimumab, certolizumab pegol, secukinumab, and ixekizumab) in 146 prescriptions (of which, 109 prescriptions were as naive) at our hospital since March 2010. Results: Throughout the entire course of the study, the 10-year retention rates were approximately 70% for adalimumab, 50% for ixekizumab, and 40% for secukinumab. When evaluating retention rates in the biologic-naïve subgroups, the 10-year retention rates were all approximately 70%. Regarding certolizumab pegol, the 3-year retention rate was approximately 75%. For adalimumab, a higher degree of arthritis at the initiation of treatment was found to correlate with an increased likelihood of secondary inefficacy. The main reason for discontinuation was secondary inefficacy, except for ixekizumab. Conclusions: Each biologic exhibited a favourable long-term retention rate. The main reason for discontinuation was secondary inefficacy. Regarding adalimumab, secondary inefficacy was linked to the extent of arthritis upon treatment initiation. [ABSTRACT FROM AUTHOR]

Certolizumab pegol (CZP; CIMZIA™) is the only Fc‐free tumor necrosis factor inhibitor with data from a clinical study demonstrating no to minimal placental transfer. The pharmacokinetics (PK) of certolizumab pegol during pregnancy and postpartum in women with chronic inflammatory diseases were assessed using a population PK model based on data from the CHERISH study (NCT04163016), a longitudinal, prospective, open‐label PK phase IB study. Model development was performed in NONMEM using a frequentist prior approach, with prior information based on a population PK model for certolizumab pegol in non‐pregnant adult patients (NCT04740814). A one‐compartment model with first‐order absorption (Ka = 0.236 1/day) and linear elimination (CL/F = 0.416 L/day) from the central compartment (V/F = 7.86 L) best described certolizumab pegol PK in the CHERISH study. The structural model parameters were estimated with good precision (RSE < 25%). Baseline BW was included as a covariate on CL/F and V/F. Pregnancy trimester and time‐varying log‐transformed anti‐drug antibody (ADA) titer were identified as the only significant covariates for CL/F with a comparable influence on CL/F. Individuals with higher ADA titer (75th percentile) during pregnancy exhibited CL/F up to 1.43‐fold higher relative to individuals postpartum that showed median levels of ADA titer. However, the confidence interval for the combined effect of pregnancy stage and ADA titer effects on CL/F overlapped with the CL/F range of the typical individual postpartum. In addition, simulations showed a large overlap in certolizumab pegol concentrations between pregnant and non‐pregnant adults. The findings of this population PK analysis support the maintenance of established certolizumab pegol dosing regimens throughout pregnancy. [ABSTRACT FROM AUTHOR]

Background: Treatment persistence among patients with psoriatic arthritis (PsA) is essential for achieving optimal treatment outcomes. Guselkumab, a fully human interleukin-23p19-subunit inhibitor, was approved by the United States (US) Food and Drug Administration for the treatment of active PsA in July 2020, with a dosing regimen of 100 mg at week 0, week 4, then every 8 weeks. In the Phase 3 DISCOVER-1 and DISCOVER-2 studies of patients with active PsA, 94% of guselkumab-randomized patients completed treatment through 1 year and 90% did so through 2 years (DISCOVER-2). Real-world evidence is needed to compare treatment persistence while following US prescribing guidelines (i.e., on-label persistence) for guselkumab versus subcutaneous (SC) tumor necrosis factor inhibitors (TNFis). Methods: Adults with PsA receiving guselkumab or their first SC TNFi (i.e., adalimumab, certolizumab pegol, etanercept, or golimumab) between 14 July 2020 and 31 March 2022 were identified in the IQVIA PharMetrics® Plus database (first claim defined the treatment start date [index date]). Baseline characteristics and biologic use (biologic-naïve/biologic-experienced) were assessed during the 12-month period preceding the index date. Baseline characteristics were balanced between cohorts using propensity-score weighting based on the standardized mortality ratio approach. The follow-up period spanned from the index date until the earlier of the end of continuous insurance eligibility or end of data availability. On-label persistence, defined as the absence of treatment discontinuation (based on a gap of 112 days for guselkumab or 56 days for SC TNFi) or any dose escalation/reduction during follow-up, was assessed in the weighted treatment cohorts using Kaplan-Meier (KM) curves. A Cox proportional hazards model, further adjusted for baseline biologic use, was used to compare on-label persistence between the weighted cohorts. Results: The guselkumab cohort included 526 patients (mean age 49.8 years; 61.2% female) and the SC TNFi cohort included 1953 patients (mean age: 48.5 years; 60.2% female). After weighting, baseline characteristics were well balanced with a mean follow-up of 12.3–12.4 months across cohorts; 51.5% of patients in the guselkumab cohort and 16.7% in the SC TNFi cohort received biologics in the 12-month baseline period. Respective rates of treatment persistence at 3, 6, 9, and 12 months were 91.2%, 84.1%, 75.9%, and 71.5% for the guselkumab cohort versus 77.3%, 61.6%, 50.0%, and 43.7% for the SC TNFi cohort (all log-rank p < 0.001). At 12 months, patients in the guselkumab cohort were 3.0 times more likely than patients in the SC TNFi cohort to remain persistent on treatment (p < 0.001). Median time to discontinuation was not reached for the guselkumab cohort and was 8.9 months for the SC TNFi cohort. Conclusion: This real-world study employing US commercial health-plan claims data to assess on-label treatment persistence in PsA demonstrated that, at 12 months, guselkumab was associated with a 3 times greater likelihood of persistence compared with SC TNFi. [ABSTRACT FROM AUTHOR]

Abstract Introduction Certolizumab pegol (CZP) is an anti-tumor necrosis factor alpha (TNFα) approved for the treatment of moderate to severe plaque psoriasis (PSO). However, data on its real-world use is currently limited. The objective of this study was to describe the 1-year real-world effectiveness of CZP, its impact on health-related quality of life (HRQoL), and safety outcomes in patients with moderate to severe PSO in multi-country settings. Methods CIMREAL, a prospective, noninterventional study, was conducted across Europe and Canada from August 2019 to December 2022. Patients were followed for 1-year, receiving CZP 400 mg initial doses at weeks 0, 2, and 4, followed by CZP 200 mg every 2 weeks (Q2W) or CZP 400 mg Q2W maintenance dosing. Effectiveness was assessed using the Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI). Safety was also evaluated. Results Overall, 399 patients with moderate to severe PSO were included. Of these, 93.7% (374/399) and 77.9% (311/399) completed months 3 and 12, respectively. Mean age (± standard deviation) was 42.9 ± 13.5 years and body mass index was 28.5 ± 6.8 kg/m2, with the majority of patients being female (68.2%). At 12 months, CZP showed substantial effectiveness, achieving PASI 75 and PASI 90 response rates (≥ 75% and ≥ 90% improvement from baseline, respectively) of 77% and 56.5%, respectively. Patients with PASI score of ≤ 3 and ≤ 2 experienced improvement from 3 months (49.8% and 41.1%, respectively) to 12 months (82.0% and 75.3%, respectively). HRQoL considerably improved, with mean DLQI scores decreasing from 12.4 to 2.3 after 12 months of treatment, and the proportion of patients with DLQI 0/1 increased from 28.6% at 3 months to 59.4% at 12 months. The 1-year probability of persistence was approximately 85%. Overall, 30.6% of the patients experienced any adverse events and 9.3% had serious adverse events. Conclusion In routine clinical practice, CZP exhibited consistent effectiveness, positively impacting both skin psoriasis activity and HRQoL. The 1-year persistence of CZP was high, and no new safety signals were identified. Trial Registration Number ClinicalTrials.gov Identifier: NCT04053881 https://www.clinicaltrials.gov/study/NCT04053881 .

Introduction: Certolizumab pegol (CZP) is an anti-tumor necrosis factor alpha (TNFα) approved for the treatment of moderate to severe plaque psoriasis (PSO). However, data on its real-world use is currently limited. The objective of this study was to describe the 1-year real-world effectiveness of CZP, its impact on health-related quality of life (HRQoL), and safety outcomes in patients with moderate to severe PSO in multi-country settings. Methods: CIMREAL, a prospective, noninterventional study, was conducted across Europe and Canada from August 2019 to December 2022. Patients were followed for 1-year, receiving CZP 400 mg initial doses at weeks 0, 2, and 4, followed by CZP 200 mg every 2 weeks (Q2W) or CZP 400 mg Q2W maintenance dosing. Effectiveness was assessed using the Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI). Safety was also evaluated. Results: Overall, 399 patients with moderate to severe PSO were included. Of these, 93.7% (374/399) and 77.9% (311/399) completed months 3 and 12, respectively. Mean age (± standard deviation) was 42.9 ± 13.5 years and body mass index was 28.5 ± 6.8 kg/m2, with the majority of patients being female (68.2%). At 12 months, CZP showed substantial effectiveness, achieving PASI 75 and PASI 90 response rates (≥ 75% and ≥ 90% improvement from baseline, respectively) of 77% and 56.5%, respectively. Patients with PASI score of ≤ 3 and ≤ 2 experienced improvement from 3 months (49.8% and 41.1%, respectively) to 12 months (82.0% and 75.3%, respectively). HRQoL considerably improved, with mean DLQI scores decreasing from 12.4 to 2.3 after 12 months of treatment, and the proportion of patients with DLQI 0/1 increased from 28.6% at 3 months to 59.4% at 12 months. The 1-year probability of persistence was approximately 85%. Overall, 30.6% of the patients experienced any adverse events and 9.3% had serious adverse events. Conclusion: In routine clinical practice, CZP exhibited consistent effectiveness, positively impacting both skin psoriasis activity and HRQoL. The 1-year persistence of CZP was high, and no new safety signals were identified. Trial Registration Number: ClinicalTrials.gov Identifier: NCT04053881 https://www.clinicaltrials.gov/study/NCT04053881. [ABSTRACT FROM AUTHOR]

Background Objectives Methods Results Conclusion Plaque psoriasis (PsO) requires long‐term treatment for symptom control and remission; thus, a long‐term pharmacological intervention is necessary. Treatment persistence reflects long‐term therapeutic effectiveness and tolerance.This study investigates drug persistence and compares treatment discontinuation rates across biologic agents and apremilast used by PsO patients in Finland and Sweden.This retrospective register‐based cohort study included bio‐naïve patients (≥18 years) with moderate‐to‐severe PsO, who initiated treatment with abatacept, adalimumab, brodalumab, certolizumab pegol, etanercept, golimumab, guselkumab, ixekizumab, risankizumab, secukinumab, tildrakizumab, ustekinumab or apremilast during 2008–2020 in Finland or Sweden. The main analysis evaluated persistence (based on duration of continuous treatment) and compared rates of treatment discontinuation using guselkumab as reference drug, during 2018–2020 in Finland. Treatment discontinuation was assessed by survival analysis of the time to first drug discontinuation, including switching to other study drugs. Due to limited sample size (n < 20), certain biologics (abatacept, brodalumab, certolizumab pegol, etanercept, golimumab, risankizumab and tildrakizumab) were excluded from the persistence analysis.In Finland, 709 patients fulfilled the inclusion criteria during 2018–2020 for the main analysis. The highest persistence was observed for guselkumab and ustekinumab with 90 and 85% of treated patients, respectively, continuing treatment for ≥1 year. Comparable results were observed in the expanded cohort analysis (index starting in 2008; 2745 bio‐naïve patients in Finland and 10,970 in Sweden). Furthermore, patients treated with guselkumab in Finland showed lower treatment discontinuation rates compared to other study drugs.Guselkumab and ustekinumab demonstrated high persistence as measured by continued treatment for at least 1 year. Furthermore, these treatments demonstrated lower rates of discontinuation compared to other study drugs included in the analysis. Understanding the balance between efficacy and feasibility in treatment decisions is crucial, as feasibility may impact persistency outcomes and potentially increase persistency rates. [ABSTRACT FROM AUTHOR]

Objective: To compare the risk of infection in inflammatory arthritis patients treated with tumor necrosis factor (TNF) inhibitors. Methods: PubMed, Embase, and the Cochrane Library were systematically searched from inception to 28 December 2023 for randomized controlled trials (RCTs) assessing TNF inhibitors and reporting infections. Subsequently, pairwise and network meta-analyses were conducted to determine odds ratios (ORs) and the corresponding 95% confidence intervals (CIs). Results: A total of 61 RCTs involving 20,458 patients were included. Pairwise meta-analysis revealed that certolizumab pegol was significantly associated with an increased risk of serious infection compared to placebo (OR:2.28, 95% CI: 1.13–4.62). Both adalimumab and certolizumab pegol were also significantly associated with an increased risk of any infection compared to placebo (OR:1.18, 95% CI: 1.06 to 1.30 and OR:1.40, 95% CI: 1.11 to 1.76, respectively). Moreover, a network meta-analysis indicated that certolizumab pegol and infliximab were associated with a higher risk of serious infection compared to other TNF inhibitors. In the cumulative ranking of any infection risk, certolizumab pegol had the highest risk compared with others. TNF inhibitors increased the risk of tuberculosis but not that of herpes zoster. Conclusion: Available evidence indicates etanercept and golimumab are likely associated with a lower risk of infection compared to other TNF inhibitors in inflammatory arthritis. For patients at a heightened risk of infection, prioritizing the use of etanercept and golimumab may be advisable to minimize patient risk. [ABSTRACT FROM AUTHOR]

ObjectivesMethodResultsConclusionThe objectives were to explore the clinical retention rate of an e-Device aimed at empowering chronic arthritis patients using certolizumab pegol (CZP) and to analyse beliefs about medication in the Danish population.Patients treated with CZP were recruited from the Netherlands, Denmark, and Sweden through rheumatology clinics at initiation of, or switching to, the e-Device. Patients were adults (aged 18–85 years) diagnosed with rheumatoid arthritis, axial spondyloarthritis, or psoriatic arthritis. Patients administered three consecutive self-injections at home. Descriptive statistics regarding baseline characteristics, retention rates, and reasons for withdrawal were assessed, along with the Beliefs about Medicines Questionnaire.In total, 59 patients participated (Netherlands 25, Denmark 15, Sweden 19). Most subjects (71%) were women, with a mean ± sd age of 55 ± 16.2 years and mean disease duration 12 ± 8.8 years. Six patients (10%) started CZP de novo and the remaining patients switched device. The overall retention rate was 42% after 52 weeks, declining to 38% after 104 weeks. A sharp decline, 34%, was seen at week 8. Between weeks 32 and 112, only four patients (6.8%) withdrew from the study. The primary reason for withdrawal was the patient’s request. Stratification by country showed significant differences for some outcomes.An initial large dropout was evident within the first 8 weeks, with almost no dropouts thereafter. The reasons for withdrawal were primarily patient requests. Thus, the injection experience must be tailored carefully when selecting patients for new autoinjector e-Devices to enhance retention rates and patient satisfaction. [ABSTRACT FROM AUTHOR]

This article explores the impact of disease-modifying antirheumatic drugs (DMARDs) on the severity of dengue in patients with rheumatoid arthritis (RA). The study, conducted in Taiwan using data from the Ministry of Health, found that RA patients on DMARDs, particularly biological/target-synthetic DMARDs (b/tsDMARDs), had a higher risk of severe outcomes such as death or hospitalization compared to non-RA patients. The research suggests that the immunosuppressive effects of DMARDs may hinder the body's ability to respond to dengue infection, leading to more severe complications. The findings are important for RA patients receiving DMARDs, especially those who are dengue-naïve travelers, as they should be aware of the potential risks and closely monitored for dengue and its complications. [Extracted from the article]

BackgroundThe EXXELERATE study revealed poorer clinical outcomes in patients treated with adalimumab (ADL) and baseline rheumatoid factor (RF) above 203 IU/mL. However, responses were similar in patients treated with certolizumab pegol (CZP) regardless of RF levels.ObjectivesThis study investigated the impact of RF levels >203 IU/mL on TNF inhibitors (TNFi) serum levels and the association with secondary nonresponse in RA patients treated with TNFi.MethodsWe performed an observational ambispective study with RA patients treated with infliximab (IFX), ADL, or CZP. Patients were stratified according to baseline RF levels: ≤ or >203 IU/mL. After 6 months, serum drug levels and antidrug antibodies were measured, and reasons for discontinuation were collected.ResultsWe included 170 RA patients: 90 (53%) received IFX, 48 (28%) ADL, and 32 (19%) CZP. While CZP serum levels did not differ between RF groups at 6 months (p = 0.6), RF levels >203 IU/mL were linked to lower serum drug levels in patients treated with IFX (p = 0.09) or ADL (p = 0.02). Secondary nonresponse was 3.6 times higher in patients with high versus low RF levels in patients under IFX or ADL. However, the reasons for withdrawal were not affected by RF levels in patients treated with CZP.ConclusionBaseline RF above 203 IU/mL is associated with lower serum drug levels and an increased risk of discontinuation due to secondary nonresponse in patients treated with IFX or ADL. In contrast, drug levels and clinical outcomes are not significantly impacted by baseline RF levels in patients under CZP.

Introduction and Objectives Certolizumab Pegol (CZP) is an anti-TNF agent approved in Brazil for Crohn's disease (CD). There is a lack of data in Brazil and Latin America detailing real-world experiences with CZP. The primary objective was clinical remission in weeks 26 and 54. The secondary endpoints were clinical response in weeks 26 and 54, endoscopic remission, biological switch rates, rates of CD-related surgery, persistence with treatment over time, and adverse events. Remission and clinical response were defined as HBI ≤4 and ≥3 points reduction of HBI, respectively. Endoscopic remission was defined as the complete healing of the intestinal mucosa.

The article discusses the clinical efficacy of abatacept, a biologic drug used to treat rheumatoid arthritis (RA), in Chinese patients. The study conducted at Zhejiang Provincial People's Hospital involved 53 RA patients who received abatacept treatment for at least 3 months. Results showed a significant decrease in disease activity scores and synovial membrane thickness after treatment, with a more pronounced effect observed in elderly patients. However, the study acknowledges limitations such as a small sample size and short duration, emphasizing the need for further research to validate these findings. [Extracted from the article]

This article discusses a study on the effectiveness and safety of risankizumab in psoriatic patients with latent tuberculosis infection (LTBI). The study found that risankizumab was effective and safe in treating psoriatic patients with LTBI, even without TB chemoprophylaxis. However, the study has limitations, such as its retrospective design and small sample size. Another document provides data on the characteristics of psoriatic patients with LTBI in Italy, including their age, gender, and prior treatments for psoriasis. This information can be useful for researchers studying the risk of tuberculosis reactivation in psoriatic patients undergoing systemic treatment. [Extracted from the article]

This article presents the findings of a retrospective study conducted in Greece to evaluate the utilization trends of biologics in patients with psoriasis. The study analyzed data from 2015 to 2020 and found that the number of psoriasis patients receiving biologic treatment more than doubled during this period. There was a decrease in the use of anti-TNF agents and an increase in the use of anti-IL prescriptions. The study also observed variations in the most prescribed drugs for different patient groups. The findings align with global trends of increasing biologic use and the gradual replacement of TNF inhibitors with IL inhibitors. The study was supported by a research grant from LEO Pharma, but the company had no involvement in the study design or data analysis. [Extracted from the article]

Abstract We report a case of a 41‐year‐old woman who developed pregnancy‐associated pyoderma gangrenosum (PG) at 4 weeks gestation. She was initially treated with prednisone, however, due to lack of improvement and risk of systemic corticosteroids in pregnancy, underwent a prednisone taper and was initiated on certolizumab pegol (CZP). The patient experienced complete wound re‐epithelialization 1 month after CZP initiation. She had no pregnancy complications except for prednisone‐associated gestational diabetes and gave birth to a healthy baby. CZP is a tumour necrosis factor‐inhibitor with negligible placental transfer and no known adverse effects in pregnancy. Its efficacy and safety for autoinflammatory dermatoses in pregnancy are very promising. This is the first case to report CZP treatment for PG in a pregnant patient.

Background and Objective: Although little information is available on the pharmacokinetics (PK) of monoclonal antibodies (mAbs) during pregnancy, multiple mAbs are being used during pregnancy for various indications. The aim of this systematic literature review was to characterize the PK of mAbs throughout pregnancy. Methods: A systematic literature search was carried out in PubMed and Embase on 21 April 2023. Articles were included when information on PK or exposure parameters of mAbs in pregnant women was available. Results: A total of 42 relevant articles were included, of which eight discussed adalimumab, three certolizumab pegol, five eculizumab, one golimumab, 12 infliximab (IFX), two natalizumab, one canakinumab, one omalizumab, five tocilizumab, eight ustekinumab, and five vedolizumab. One of the 42 studies reported information on clearance (CL) and volume of distribution (VD) of IFX; all other studies only reported on serum concentrations in the pre-pregnancy state, different trimesters, and the postpartum period. For all of the assessed mAbs except IFX, serum concentrations were similar to concentrations in the pre-pregnancy state or modestly decreased. In contrast, IFX trough concentrations generally increased in the second and third trimesters in comparison to the non-pregnant state. Conclusion: Available information suggests that the anatomical and physiological changes throughout pregnancy may have meaningful effects on the PK of mAbs. For most mAbs (not IFX), modestly higher dosing (per mg) maybe needed during pregnancy to sustain a similar serum exposure compared to pre-pregnancy. [ABSTRACT FROM AUTHOR]

Introduction: Spondyloarthritis (SpA) is a group of chronic inflammatory diseases, often affecting women in reproductive age, which can have a significant impact on the reproductive health of women. Preconception counselling and medication adjustments have shown to reduce flares and improve pregnancy outcomes in women with rheumatoid arthritis. However, in women with SpA, data of the impact of preconception counselling on pregnancy outcomes is scarce. The aim of this study is to evaluate its impact. Methods: In this retrospective multicentric study, data was collected from medical records of women who gave birth from 2020 to 2022. The study included 45 pregnancies, which were divided into two categories - whether they received preconception consultation or not. Data was collected on patient characteristics, disease duration, medications used, and preconception counselling. Maternal and foetal outcomes were studied. Results: In this study involving 45 patients, radiographic axial spondyloarthritis was the most prevalent type (16 cases), with psoriatic arthritis showing the highest preconception consultation rate (80.0%), with an average of 33.90 years. Lower rates of contraindicated medication were used during pregnancy (0.0%) in counselled patients versus those without counselling (20.0%). Sulfasalazine usage was higher in non-counselled patients (77.8%), while certolizumab pegol use was higher in counselled patients (33.3%). Pregnancy outcomes showed no significant difference in successful pregnancies, but counselled patients experienced significantly fewer postpartum flares (6.4% vs 36.6%). Gestational age at delivery and newborn weight did not significantly differ between groups. Foetal malformation occurred in 2.6% of the population, with no significant difference based on counselling status. Conclusion: Preconception counselling in women with SpA can increase the likelihood of medication adjustments before pregnancy and decrease the occurrence of flares postpartum. These findings suggest that preconception counselling should be implemented in the management of pregnant women with SpA to improve pregnancy outcomes. Further studies are needed to confirm the effectiveness of preconception counselling and to determine the optimal approach. [ABSTRACT FROM AUTHOR]

Objective: We investigated methotrexate safety and the influence of dose on efficacy outcomes in combination with three different biologic treatments and with active conventional treatment (ACT) in early rheumatoid arthritis (RA). Methods: This post hoc analysis included 812 treatment‐naïve patients with early RA who were randomized (1:1:1:1) in the NORD‐STAR trial to receive methotrexate in combination with ACT, certolizumab‐pegol, abatacept, or tocilizumab. Methotrexate safety, doses, and dose effects on Clinical Disease Activity Index (CDAI) remission were assessed after 24 weeks of treatment. Results: Compared with ACT, the prevalence of methotrexate‐associated side effects was higher when methotrexate was combined with tocilizumab (hazard ratio [HR] 1.48, 95% confidence interval [CI] 1.20–1.84) but not with certolizumab‐pegol (HR 0.99, 95% CI 0.79–1.23) or with abatacept (HR 0.93, 95% CI 0.75–1.16). With ACT as the reference, the methotrexate dose was significantly lower when used in combination with tocilizumab (β −4.65, 95% CI −5.83 to −3.46; P < 0.001) or abatacept (β −1.15, 95% CI −2.27 to −0.03; P = 0.04), and it was numerically lower in combination with certolizumab‐pegol (β −1.07, 95% CI −2.21 to 0.07; P = 0.07). Methotrexate dose reductions were not associated with decreased CDAI remission rates within any of the treatment combinations. Conclusion: Methotrexate was generally well tolerated in combination therapies, but adverse events were a limiting factor in receiving the target dose of 25 mg/wk, and these were more frequent in combination with tocilizumab versus ACT. On the other hand, methotrexate dose reductions were not associated with decreased CDAI remission rates within any of the four treatment combinations at 24 weeks. [ABSTRACT FROM AUTHOR]

Introduction: Patients with psoriasis who have failed multiple biologic drugs have been defined as "multi‐failure," although there are no clear data on the characteristics, comorbidities, and best treatment strategies for this population. Nowadays, given the next generation and the number of biologics available, patients are considered multi‐failure when ≥4 biologics fail to achieve a good response. Methods: Demographic characteristics and efficacy of anti‐interleukin drugs in multi‐failure patients were compared to a cohort of general psoriatic patients treated with IL‐23 or IL‐17 inhibitors. Results: In total 97 multi‐failure patients (≥4 lines of biologics) were compared with 1,057 patients in the general cohort. The current drugs in the multi‐failure group were risankizumab (34), ixekizumab (23), guselkumab (21), brodalumab (7), tildrakizumab (5), ustekinumab (4), secukinumab (2), and certolizumab pegol (1). A significant difference was found in the multi‐failure cohort for age of psoriasis onset (mean 29.7 vs. 35.1, P < 0.001), concurrent psoriatic arthritis (45.4 vs. 26.9%, P < 0.001), diabetes mellitus (30.9 vs. 10.9%, P < 0.001), and cardiovascular comorbidity (54.6 vs. 39.8%, P = 0.005). In multi‐failure patients, current biological therapy showed a good initial response (PASI 90 and 100 of 41.24 and 27.84%, respectively, at 16 weeks); the response tended to decline after 40 weeks. Anti‐IL‐17 agents showed clinical superiority over IL‐23 agents in terms of achieving PASI90 at 28 weeks (P < 0.001) and 40 weeks (P = 0.007), after which they reached a plateau. In contrast, IL‐23 agents showed a slower but progressive improvement that was maintained for up to 52 weeks. A similar trend was also seen for PASI100 (28 weeks P = 0.032; 40 weeks P = 0.121). Conclusions: The multi‐failure patient is characterized by many comorbidities and longstanding inflammatory disease that frequently precedes the introduction of systemic biologic therapy. Further studies are needed to identify more specific criteria that could be applied as a guideline by clinicians. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To investigate the effects of both the Fc fragment in tumor necrosis factor (TNF) inhibitors and rheumatoid factor (RF) titers on treatment survival, disease activity, and laboratory parameters in patients with rheumatoid arthritis (RA). METHODS: In this retrospective cohort study, patients with RA who had started any anti-TNF therapy between January 2017 and March 2020 and who had stayed on this treatment for at least six months were included. The data of the patients were compared separately according to continuation or discontinuation of treatment and the presence or absence of Fc portion in the structure of anti-TNFs. Patients who were taking certolizumab pegol (CZP) without the Fc fragment were placed in the “without Fc group” (wo/Fc), while patients who were taking other drugs (adalimumab, etanercept, golimumab, and infliximab) were placed in the “with Fc group” (w/Fc). RESULTS: Among the 221 RA patients whose data were available, 52 patients met the inclusion criteria and were included in the study. There was a significant difference in the DAS28-CRP score between wo/Fc group and w/Fc group in the third month of treatment (p=0.012). However, this difference did not persist at the sixth month of treatment (p=0.384). According to the cox-regression results, RF titers were determined to have a significant impact on the drug survival of anti-TNF agents when adjustments were made for the effects of other candidate predictors (Hazard ratio: 1.007 (1.002–1.012), p=0.009). CONCLUSION: Our results suggest that compared to the Fc fragment, RF titers were the more important risk factor in survival of anti-TNF drugs. [ABSTRACT FROM AUTHOR]

This article discusses a series of 10 cases where patients with psoriasis developed paradoxical eczema (PE) exclusively on their ears after being treated with biologic drugs. The patients experienced the onset of PE at different times after starting biologic therapy, with a median time of 12 months. The implicated biologics included tumor necrosis factor (TNF) inhibitors, anti-interleukin (IL)-17 drugs, and anti-IL-23p19 drugs. Treatment with topical steroids and systemic therapy was successful for some patients, while others had to discontinue their current biologic treatment or switch to a different class of biologic. The duration of eczema before resolution varied depending on the treatment approach. The article suggests that the pathogenesis of PE may be related to the mechanism of action of the involved drugs and alterations in the skin microbiome. Further research is needed to better understand this phenomenon. [Extracted from the article]

This article discusses the use of off-label biologic treatments for refractory inflammatory scarring alopecia. Scarring alopecias are a group of diseases that result in permanent hair loss. The article provides a review of different off-label systemic treatments for conditions such as dissecting cellulitis of the scalp, folliculitis decalvans, lichen planopilaris, and frontal fibrosing alopecia. The treatments mentioned include adalimumab, guselkumab, secukinumab, risankizumab, tildrakizumab, and certolizumab. The article concludes that while these case reports offer hope for affected patients, controlled clinical trials are needed to fully understand the effectiveness and potential side effects of these treatments. [Extracted from the article]

Background: Cicatricial alopecia (CA) refers to various conditions that result in permanent hair loss. Treatment of CA has always been challenging. Regarding immune-mediated pathophysiology for many CA subtypes, the administration of Janus kinase (JAK) and tumor necrosis factor (TNF) inhibitors have potentiated the treatments of CA. Methods: After a thorough systematic search in PubMed/Medline, Embase, Web of Science, Scopus, Google Scholar, ClinicalTrials.gov, and WHO ICTRP, a total of 3,532 relevant records were retrieved and screened. Accordingly, 56 studies met the eligibility criteria and entered the review. Results: Among JAK inhibitors, oral tofacitinib was the most frequently reported and the most effective treatment in improving signs and symptoms of CA with minimal adverse effects (AEs). Baricitinib was another JAK inhibitor with sustained improvement while causing mild AEs. As a TNF inhibitor, adalimumab induced a rapid and stable improvement in signs and symptoms in most patients with rare, tolerable AEs. Thalidomide was the other frequently reported yet controversial TNF inhibitor, which caused a rapid and significant improvement in the condition. However, it may result in mild to severe AEs, particularly neuropathies. Infliximab is a TNF inhibitor with mostly favorable results, albeit in a few patients caused treatable dermatological AEs. Apremilast and certolizumab pegol caused an incomplete amelioration of signs and symptoms with no AEs. Lenalidomide is another TNF inhibitor that can induce temporary improvement in CA with probable AEs. It is noteworthy that utilizing adalimumab, infliximab, etanercept, golimumab, and an anonymous TNF inhibitor has induced paradoxical CA and other A.E.s in some patients. Conclusion: Recent studies have recommended JAK and TNF inhibitors, especially oral tofacitinib and adalimumab, as a new modality or adjuvant therapy to previous medications for primary CA. Nonetheless, monitoring AEs on a regular basis is suggested, and further extensive studies are required before definitive recommendations. [ABSTRACT FROM AUTHOR]

Disease-modifying anti-rheumatic drugs (DMARDs) is a class of anti-rheumatic medicines that are frequently prescribed to patients suffering from rheumatoid arthritis (RA). Methotrexate, sulfasalazine, hydroxychloroquine, and azathioprine are examples of non-biologic DMARDs that are being used for alleviating pain and preventing disease progression. Biologic DMARDs (bDMARDs) like infliximab, rituximab, etanercept, adalimumab, tocilizumab, certolizumab pegol, and abatacept have greater effectiveness with fewer adverse effects in comparison to non-biologic DMARDs. This review article delineates the classification of DMARDs and their characteristic attributes. The poor aqueous solubility or permeability causes the limited oral bioavailability of synthetic DMARDs, while the high molecular weights along with the bulky structures of bDMARDs have posed few obstacles in their drug delivery and need to be addressed through the development of nanoformulations like cubosomes, nanospheres, nanoemulsions, solid lipid nanoparticles, nanomicelles, liposome, niosomes, and nanostructured lipid carrier. The main focus of this review article is to highlight the potential role of nanotechnology in the drug delivery of DMARDs for increasing solubility, dissolution, and bioavailability for the improved management of RA. This article also focusses on the different aspects of nanoparticles like their applications in biologics, biocompatibility, body clearance, scalability, drug loading, and stability issues. [ABSTRACT FROM AUTHOR]

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Biological therapies may act as immunogenic triggers leading to the formation of anti-drug antibodies (ADAs). Population pharmacokinetic (PK) models can be used to characterize the relationship between ADA and drug disposition but often rely on the ADA bioassay results, which may not be sufficiently sensitive to inform on this characterization. In this work, a methodology that could help to further elucidate the underlying ADA production and impact on the drug disposition was explored. A mixed hidden-Markov model (MHMM) was developed to characterize the underlying (hidden) formation of ADA against the biologic, using certolizumab pegol (CZP), as a test drug. CZP is a PEGylated Fc free TNF-inhibitor used in the treatment of rheumatoid arthritis and other chronic inflammatory diseases. The bivariate MHMM used information from plasma drug concentrations and ADA measurements, from six clinical studies (n = 845), that were correlated through a bivariate Gaussian function to infer about two hidden states; production and no-production of ADA influencing PK. Estimation of inter-individual variability was not supported in this case. Parameters associated with the observed part of the model were reasonably well estimated while parameters associated with the hidden part were less precise. Individual state sequences obtained using a Viterbi algorithm suggested that the model was able to determine the start of ADA production for each individual, being a more assay-independent methodology than traditional population PK. The model serves as a basis for identification of covariates influencing the ADA formation, and thus has the potential to identify aspects that minimize its impact on PK and/or efficacy. [ABSTRACT FROM AUTHOR]

The objectives of our study were to assess retention rate, safety, and predictive factors for retention of subcutaneous (SC) TNF inhibitors (TNFi) (adalimumab (ADA), etanercept (ETN), golimumab (GOL), and certolizumab pegol (CZP)) in axial spondyloarthritis (axSpA) depending on the line of treatment in real-life conditions. A multicentre retrospective observational study was conducted including 552 patients fulfilling the ASAS criteria for axSpA followed in the RIC-France register who began SC-TNFi between 01/01/13 and 08/31/2018 for a total of 824 prescriptions. Taking all lines of treatment into account, GOL had a significantly higher retention rate compared with ADA, ETN, and CZP with a mean retention length of 59 months. As first-line bDMARDs, GOL had a significantly higher retention rate compared with ADA and ETN. ETN had the best retention rate when prescribed as at least 3rd bDMARD. Taking all lines of treatment into account, female sex, peripheral disease, BASDAI at initiation, and line of treatment were predictive factors for treatment cessation. Primary inefficiency was the most frequent reason for treatment cessation. In conclusion, GOL showed the highest retention rate in axSpA. Male sex, absence of peripheral disease, and early line of prescription were associated with better SC-TNFi retention in axSpA. [ABSTRACT FROM AUTHOR]

Tumor necrosis factor alpha (TNFα) inhibitors are now widely used to treat immune‐mediated inflammatory diseases. Although they have a good safety profile, they are also associated with adverse cutaneous events. Pigmented purpuric dermatoses (PPD) include a variety of skin diseases characterized by multiple petechial hemorrhages due to capillaritis. Five major clinical types of PPD have been described and purpura annularis telangiectodes of Majocchi (PATM) is a rare subtype of PPD. The cause of PPD is unknown, but drugs are implicated in a minority of cases. There are very few cases in the literature triggered by TNFα inhibitors. We present a case of PATM induced by certolizumab pegol and perform a review including 4 articles in the literature reporting 5 PPD cases induced by TNFα inhibitors. When purpuric eruptions develop in patients treated with TNFα inhibitors, PPD and vasculitis should be differentiated. Thus, patients are not exposed to unnecessary evaluations and treatments. [ABSTRACT FROM AUTHOR]

Although biologics have their own characteristics, there are no clear criteria for selecting them to treat the patients with rheumatoid arthritis. To assist in selecting biologics, we investigated the retention rates of biologics at our institution. We examined retention rates, and reasons for dropout for biologics in 393 cases and 605 prescriptions (of which 378 prescriptions were as naive) at our hospital since October 2003. Throughout the entire course of the study, etanercept (ETN) was the most frequently used biologic, followed by adalimumab (ADA) and tocilizumab (TCZ). When narrowed down to the later period from 2010, ETN was still the most used, followed by TCZ and abatacept (ABT). When the retention rates were compared in biologic naive patients, the retention rates were TCZ, ABT, ETN, certolizumab pegol (CZP), golimumab (GLM), infliximab (IFX), and ADA, in that order. The retention rates were better with the first use of each biologic. The main reasons for dropout were primary ineffectiveness, secondary ineffectiveness, and infection. ETN was the most used biologic in our hospital, with an increasing trend toward the use of non-TNF inhibitors. Retention rates were higher in non-TNF inhibitors. [ABSTRACT FROM AUTHOR]

Objectives: The aim is to clarify the differences in magnetic resonance imaging (MRI) findings between rheumatoid arthritis (RA) patients treated with certolizumab pegol (CZP) and infliximab (IFX). Methods: The study included RA patients who received CZP or IFX and were examined with low-field MRI (compacTscan; compact magnetic resonance imaging) at the beginning and again within 6 months of treatment initiation. Comparisons were made regarding background, clinical course, and differences in MRI findings following initiation of tumour necrosis factor inhibitors between the CZP and IFX treatment groups. MRI findings were evaluated by scoring erosion, bone marrow oedema (BME), and synovitis. Results: Ten cases in CZP and 18 cases in IFX group were compared. The biologic disease-modifying antirheumatic drug-naïve rate in the IFX group was significantly higher than that in the CZP group. After 6 months, disease activities were significantly decreased from baseline in both groups. Erosion score did not change significantly in both groups after 6 months. BME score was significantly decreased in the CZP group after 6 months, whereas in the IFX group, there was no significant change. Synovitis score was significantly decreased in both groups after 6 months. Conclusions: The findings of our study suggest that, in patients with RA, CZP might improve BME more effectively than IFX. [ABSTRACT FROM AUTHOR]

Inflammatory rheumatic diseases usually affect women of childbearing age treated with biologic drugs. However, there is a lack of literature on the efficacy and toxicity of biologic disease-modifying drugs during pregnancy. The aim of this study was to determine the presence of pregnant patients treated with bDMARDs in a real-world dataset and to examine the impact of pregnancy and lactation on the evolution of rheumatic disease in a registry of Spanish patients. This was a multicentre prospective study with a real-world setting. Information was obtained from BIOBADASER registry. Patients included are women who got pregnant until November 2020 from 19 rheumatology units. We conducted proportions, means, and standard deviations (SD) to describe the study population and the use of treatments. T -test and Chi-square test were applied to assess differences between groups. Ninety cases of pregnancy were registered (n = 68 full-term pregnancies; n = 22 spontaneous miscarriages). Most of the cases discontinued bDMARDs during pregnancy (78.9%) but 13 cases continued treatment during pregnancy, mainly using certolizumab pegol. These cases were obtaining better management of rheumatic disease, although the differences were not statistically significant [DAS28-CRP, 2.9 (SD: 1.6) vs. 2.0 (1.2), p =.255; DAS28-ESR, 2.2 (1.0) vs. 1.7 (.5), p =.266]. No serious adverse events were reported during pregnancy and lactation. Being pregnant is still an uncommon condition in patients with rheumatic diseases and using bDMARDs. Our results show that rheumatic disease tended to progress better during pregnancy in patients who continued to take bDMARDs. [ABSTRACT FROM AUTHOR]

Such standardization would improve interpretation of results, which may help healthcare practitioners utilize real-world treatment data to make treatment decisions for patients with psoriasis. Furthermore, this definition of "remission" does not consider the wide variety of factors that contribute to treatment patterns, including loss of insurance coverage or termination of systemic therapies while a patient is pregnant. Therefore, it would be helpful to include sensitivity analyses using treatment gap definitions independent of dosing schedules in future studies measuring treatment persistence. Furthermore, when assessing treatment patterns using administrative claims databases, one should consider evaluating both adherence, which measures the actual days on treatment without counting the gaps, and persistence to provide a more comprehensive assessment of real-world treatment effectiveness. [Extracted from the article]

Background: Psoriasis is a chronic immune-mediated inflammatory systemic disease with skin manifestations characterized by erythematous, scaly, itchy and/ or painful plaques resulting from hyperproliferation of keratinocytes. Certolizumab pegol [CZP], a PEGylated antigen binding fragment of a humanized monoclonal antibody against TNF-alpha, is approved for the treatment of moderate-to-severe plaque psoriasis. Patients with psoriasis present clinical and molecular variability, affecting response to treatment. Herein, we utilized an in silico approach to model the effects of CZP in a virtual population (vPop) with moderate-to-severe psoriasis. Our proof-of-concept study aims to assess the performance of our model in generating a vPop and defining CZP response variability based on patient profiles. Methods: We built a quantitative systems pharmacology (QSP) model of a clinical trial-like vPop with moderate-to-severe psoriasis treated with two dosing schemes of CZP (200 mg and 400 mg, both every two weeks for 16 weeks, starting with a loading dose of CZP 400 mg at weeks 0, 2, and 4). We applied different modelling approaches: (i) an algorithm to generate vPop according to reference population values and comorbidity frequencies in real-world populations; (ii) physiologically based pharmacokinetic (PBPK) models of CZP dosing schemes in each virtual patient; and (iii) systems biology-based models of the mechanism of action (MoA) of the drug. Results: The combination of our different modelling approaches yielded a vPop distribution and a PBPK model that aligned with existing literature. Our systems biology and QSP models reproduced known biological and clinical activity, presenting outcomes correlating with clinical efficacy measures. We identified distinct clusters of virtual patients based on their psoriasis-related protein predicted activity when treated with CZP, which could help unravel differences in drug efficacy in diverse subpopulations. Moreover, our models revealed clusters of MoA solutions irrespective of the dosing regimen employed. Conclusion: Our study provided patient specific QSP models that reproduced clinical and molecular efficacy features, supporting the use of computational methods as modelling strategy to explore drug response variability. This might shed light on the differences in drug efficacy in diverse subpopulations, especially useful in complex diseases such as psoriasis, through the generation of mechanistically based hypotheses. [ABSTRACT FROM AUTHOR]

Background: Biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) are highly effective in treating rheumatoid arthritis (RA), albeit high drug cost has restricted their use in many countries. As a countermeasure, Norway implemented pharmaceutical tendering as a cost-reducing strategy. The aim of this study was to assess the annual proportion of different b/tsDMARDs registered to treat RA patients under the influence of a Norwegian pharmaceutical tendering between 2010 and 2019. Method: The data is collected from ten Norwegian outpatient centers. The included patients are categorized as naïve, non-naïve, and current b/tsDMARD users. 13 individual b/tsDMARDs are assessed and compared with the tender rankings from each year. Overview of subcutaneous (sc) with per oral vs. intravenous (iv) and biosimilars vs. non-biosimilar are also described. Result: The tender-winning b/tsDMARD was the most or second most used drug in nine out of ten years for naïve users, seven for non-naïve users, and twice for current users. The average sum of the highest and second highest proportion among naïve, non-naïve, and current b/tsDMARD users were 75%, 53%, and 50% during the ten years, respectively. The tender-winning drug was iv in eight out of ten years. However, the average total proportion of sc and per oral b/tsDMARDs was about 70% for naïve b/tsDMARD users, 50% for non-naïve b/tsDMARD users, and 60% for current b/tsDMARD users. The main contributors to sc and per oral b/tsDMARD were etanercept (reference and biosimilar) and certolizumab pegol. The main contributors to iv b/tsDMARD were rituximab reference and infliximab biosimilar. Despite low-ranking offers, rituximab reference (offered as a second-line drug) often achieved a high proportion among non-naïve and current b/tsDMARD users. After the introduction of biosimilars, their average proportion was about 40%, 40%, and 20% for naïve, non-naïve, and current b/tsDMARD users, respectively. Conclusion: Based on observed data, a higher tender rank was associated with a higher proportion among naïve and non-naïve b/tsDMARD users. However, in most cases, sc b/tsDMARDs achieved a higher proportion with lower tender ranks than iv b/tsDMARDs with higher tender ranks. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Endoscopic healing has been associated with improved long-term clinical outcomes in inflammatory bowel disease (IBD) and is a recommended target for treatment. Evidence is limited regarding real-world uptake and patterns of treat-to-target monitoring to assess endoscopic healing after treatment initiation. We aimed to estimate the proportion of patients in the Study of a Prospective Adult Research Cohort with IBD (SPARC IBD) who received colonoscopy in the 3-15 months after starting a new IBD treatment. METHODS: We identified SPARC IBD patients who initiated a new biologic (infliximab, adalimumab, certolizumab pegol, golimumab, vedolizumab, and ustekinumab) or tofacitinib. We estimated the proportion of patients who received colonoscopies in the 3-15 months after IBD treatment initiation and described use by patient subgroups. RESULTS: Among 1,708 eligible initiations from 2017 to 2022, the most common medications were ustekinumab (32%), infliximab (22%), vedolizumab (20%), and adalimumab (16%). The median patient age was 38 years, with 66% Crohn's disease; 55% were female, and 12% were non-White. In the 3-15 months after medication initiation, 49.3% (95% confidence interval 46.2%-52.5%) of initiations were followed by a colonoscopy. Colonoscopy use was similar between ulcerative colitis and Crohn's disease, but was higher among male patients, those older than 40 years, and those who received colonoscopy within 3 months of initiation. Colonoscopy use varied between study sites, from 26.6% (15.0%-38.3%) to 63.2% (54.5%-72.0%). DISCUSSION: Approximately half of SPARC IBD patients received colonoscopy in the 3-15 months after initiation to a new IBD treatment, suggesting a low uptake of treat-to-target colonoscopy for the assessment of mucosal healing in real-world clinical practice. The variation in colonoscopy use between study sites suggests a lack of consensus and a need for more robust evidence around whether or not the practice of routine monitoring colonoscopy is associated with improved patient outcomes. [ABSTRACT FROM AUTHOR]

Abstract Introduction This study aimed to retrospectively examine the drug survival of tumor necrosis factor (TNF)-alpha inhibitors and switched subsequent biologic agents after discontinuation of TNF inhibitors. Methods This real-world setting study was conducted at a single academic center. We included patients who were treated with adalimumab (n = 111), certolizumab pegol (n = 12), and infliximab (n = 74) at Jichi Medical University Hospital from 1 January 2010 to 31 July 2021. Results No significant differences were noted in drug survival between the three TNF inhibitors. The 10-year drug survival rate for adalimumab and infliximab was 14% and 18%, respectively. Of the patients who discontinued TNF inhibitors for any reason (n = 137), 105 chose biologics as their subsequent treatment. The subsequent biologics included 31 cases of TNF inhibitors (adalimumab in 20, certolizumab pegol in 1, and infliximab in 10), 19 of interleukin-12/23 inhibitor (ustekinumab), 42 of interleukin-17 inhibitors (secukinumab in 19, brodalumab in 9, and ixekizumab in 14) and 13 of interleukin-23 inhibitors (guselkumab in 11, risankizumab in 1, and tildrakizumab in 1). Cox proportional hazards analysis for the subsequent drugs in cases of discontinuation due to inadequate efficacy revealed that female sex was a predictor of drug discontinuation (hazard ratio 2.58, 95% confidence interval 1.17–5.70) and that taking interleukin-17 inhibitors rather than TNF inhibitors was a predictor of drug persistence (hazard ratio 0.37, 95% confidence interval 0.15–0.93). Conclusions Interleukin-17 inhibitors may be a favorable option for patients who need to switch from TNF inhibitors due to inadequate efficacy. However, this study is limited by the small number of cases and its retrospective design.

Abstract Certolizumab pegol (CZP) is a Fab’ fragment of the humanized antibody with anti-TNF-α activity that is indicated as therapy for Crohn’s disease and rheumatoid arthritis. Using a BioSep-SEC-S3000 column (300 x 4.6 mm i.d., 5 µm particle size), a size exclusion liquid chromatography (SEC) method was developed. Mobile phase A consisted of 100 mM monobasic sodium phosphate and 200 mM sodium chloride (pH 7.0), while mobile phase B was ethanol (95:5, v/v), and the analysis was performed using a diode array detector (DAD) set to 214 nm and a flow rate of 0.5 ml min-1. In addition, a reversed-phase liquid chromatography (RP-LC) method based on gradient elution was developed on a Zorbax 300 SB C18 column (150 mm x 4.6 mm i.d., 3.5 µm particle size) kept at 80 °C. Mobile phase A was 0.1% (v/v) TFA in ultrapure water, and mobile phase B was a mixture of propanol, acetonitrile, ultrapure water and TFA (70 + 20 + 9.9 + 0.1, v/v) operated at a flow rate of 1.0 ml min-1, and DAD was applied at 214 nm. CZP elution was achieved with retention times of 5.6 min and 9.0 min for SEC and RP-LC, respectively.

BackgroundPsoriasis is a chronic immune-mediated inflammatory systemic disease with skin manifestations characterized by erythematous, scaly, itchy and/or painful plaques resulting from hyperproliferation of keratinocytes. Certolizumab pegol [CZP], a PEGylated antigen binding fragment of a humanized monoclonal antibody against TNF-alpha, is approved for the treatment of moderate-to-severe plaque psoriasis. Patients with psoriasis present clinical and molecular variability, affecting response to treatment. Herein, we utilized an in silico approach to model the effects of CZP in a virtual population (vPop) with moderate-to-severe psoriasis. Our proof-of-concept study aims to assess the performance of our model in generating a vPop and defining CZP response variability based on patient profiles.MethodsWe built a quantitative systems pharmacology (QSP) model of a clinical trial-like vPop with moderate-to-severe psoriasis treated with two dosing schemes of CZP (200 mg and 400 mg, both every two weeks for 16 weeks, starting with a loading dose of CZP 400 mg at weeks 0, 2, and 4). We applied different modelling approaches: (i) an algorithm to generate vPop according to reference population values and comorbidity frequencies in real-world populations; (ii) physiologically based pharmacokinetic (PBPK) models of CZP dosing schemes in each virtual patient; and (iii) systems biology-based models of the mechanism of action (MoA) of the drug.ResultsThe combination of our different modelling approaches yielded a vPop distribution and a PBPK model that aligned with existing literature. Our systems biology and QSP models reproduced known biological and clinical activity, presenting outcomes correlating with clinical efficacy measures. We identified distinct clusters of virtual patients based on their psoriasis-related protein predicted activity when treated with CZP, which could help unravel differences in drug efficacy in diverse subpopulations. Moreover, our models revealed clusters of MoA solutions irrespective of the dosing regimen employed.ConclusionOur study provided patient specific QSP models that reproduced clinical and molecular efficacy features, supporting the use of computational methods as modelling strategy to explore drug response variability. This might shed light on the differences in drug efficacy in diverse subpopulations, especially useful in complex diseases such as psoriasis, through the generation of mechanistically based hypotheses.

Background: Patients with active axial spondyloarthritis (axSpA) exhibit more absences and lower levels of productivity in the workplace and household than the general population, which can improve upon treatment. Objectives: The objective of this study is to determine the long-term impact of achieving different levels of clinical response or disease activity on workplace and household productivity in patients with axSpA. Design: RAPID-axSpA (NCT01087762) was a 204-week phase III trial evaluating the safety and efficacy of certolizumab pegol (CZP) in adult patients with active axSpA. Methods: The impact of axSpA on workplace and household productivity was evaluated using the validated arthritis-specific Work Productivity Survey. Outcomes included the percentage of patients achieving Assessment of SpondyloArthritis International Society (ASAS) response and Ankylosing Spondylitis Disease Activity Score (ASDAS) thresholds. This post hoc study used a generalised estimating equations model to determine the association between the threshold of clinical response achieved and patient productivity. Results: Of 218 CZP-randomised patients, 65.1% completed week 204. At baseline, 72.0% were employed outside the home. Of the patients who were unemployed, 42.6% were unable to work due to arthritis. Achievement of higher treatment response thresholds, such as clinical remission, was associated with fewer days affected by workplace absenteeism (ASAS-partial remission: 4.0 days, ASAS40: 8.6 days, ASAS20 but not reaching ASAS40 response: 29.4 days, ASAS20 non-response: 69.2 days; ASDAS-inactive disease: 5.0 days, ASDAS-low disease activity: 15.6 days, ASDAS-high disease activity: 32.7 days, ASDAS-very high disease activity: 93.4 days). Similar associations were found for workplace presenteeism, and household absenteeism and presenteeism. Conclusions: Over 4 years, achievement of higher clinical response thresholds and lower levels of disease activity was associated with fewer cumulative days affected by absenteeism or presenteeism, with clinical remission associated with the greatest improvements in productivity. This highlights the importance of targeting these thresholds to limit the burden of axSpA on society and on patients' daily lives. [ABSTRACT FROM AUTHOR]

Introduction: Tumor necrosis factor (TNF) inhibitors (adalimumab, infliximab, etanercept, golimumab, and certolizumab pegol) have revolutionized the treatment of severe immune-mediated inflammatory diseases, including rheumatoid arthritis, Crohn’s disease, psoriatic arthritis, ankylosing spondylitis, and ulcerative colitis. This study assessed adverse drug reactions (ADRs) after the use of TNFα inhibitors in VigiAccess of the World Health Organization (WHO) and compared the adverse reaction characteristics of five inhibitors to select the drug with the least risk for individualized patient use. Methods: The study was a retrospective descriptive analysis method in design. We sorted out five marketed anti-TNFα drugs, and their ADR reports were obtained from WHO-VigiAccess. Data collection included data on the age groups, sex, and regions of patients worldwide covered by ADR reports, as well as data on disease systems and symptoms caused by ADRs recorded in annual ADR reports and reports received by the WHO. By calculating the proportion of adverse reactions reported for each drug, we compared the similarities and differences in adverse reactions for the five drugs. Results: Overall, 1,403,273 adverse events (AEs) related to the five anti-TNFα agents had been reported in VigiAccess at the time of the search. The results show that the 10 most commonly reported AE manifestations were rash, arthralgia, rheumatoid arthritis, headache, pneumonia, psoriasis, nausea, diarrhea, pruritus, and dyspnea. The top five commonly reported AE types of anti-TNFα drugs were as follows: infections and infestations (184,909, 23.0%), musculoskeletal and connective tissue disorders (704,657, 28.6%), gastrointestinal disorders (122,373, 15.3%), skin and subcutaneous tissue disorders (108,259, 13.5%), and nervous system disorders (88,498, 11.0%). The preferred terms of myelosuppression and acromegaly were obvious in golimumab. Infliximab showed a significantly higher ADR report ratio in the infusion-related reaction compared to the other four inhibitors. The rate of ADR reports for lower respiratory tract infection and other infections was the highest for golimumab. Conclusion: No causal associations could be established between the TNFα inhibitors and the ADRs. Current comparative observational studies of these inhibitors revealed common and specific adverse reactions in the ADR reports of the WHO received for these drugs. Clinicians should improve the rational use of these high-priced drugs according to the characteristics of ADRs. [ABSTRACT FROM AUTHOR]

Aim: Certolizumab pegol (CZP), an Fc‐free, PEGylated tumor necrosis factor inhibitor (TNFi), has shown rapid and sustained reduction in signs and symptoms of rheumatoid arthritis (RA). Elevated rheumatoid factor (RF) level has been associated with RA disease progression and poorer TNFi response. We assessed the efficacy of CZP in patients with early and established RA across baseline RF levels. Methods: This post‐hoc analysis included data from 6 trials: C‐OPERA (NCT01451203), pooled RAPID trials (RAPID‐1 [NCT00152386], RAPID‐2 [NCT00160602], J‐RAPID [NCT00791999], RAPID‐C [NCT02151851]), and EXXELERATE (NCT01500278). Patients who received CZP or placebo/comparator with methotrexate (MTX) were categorized by baseline RF quartiles. Efficacy was assessed with Disease Activity Score‐28 erythrocyte sedimentation rate (DAS28‐ESR). Results: Overall, 316, 1537, and 908 patients were included in C‐OPERA, pooled RAPID trials, and EXXELERATE, respectively. Patient demographics and baseline disease characteristics were similar between treatment groups and across RF quartiles. DAS28‐ESR low disease activity (LDA) and remission (REM) rates were numerically higher in the CZP + MTX group than PBO + MTX group at weeks 12 and 24, across RF quartiles. LDA and REM rates in the CZP + MTX groups were comparable across RF quartiles at weeks 12 and 24. Mean DAS28‐ESR decreased from week 0 to week 24 in the CZP + MTX groups, across RF quartiles. Conclusion: CZP showed steady efficacy across baseline RF quartiles in patients with early and established RA, over 24 weeks. CZP treatment may be considered in patients with RA irrespective of baseline RF levels and time from diagnosis. [ABSTRACT FROM AUTHOR]

Within the past two decades, biologic therapy has become vital in the management of several refractory inflammatory dermatoses. Diagnoses for which biologic therapy was initiated included: atopic dermatitis (AD) (53%), psoriasis (30%), Crohn's disease (12%), and hidradenitis suppurativa (6%). Development of cutaneous T-cell lymphoma following exposure to biologic therapy: a Mayo Clinic retrospective analysis. [Extracted from the article]

Rheumatoid arthritis, RA, is a chronic autoimmune disease characterized by joint pain, tenderness, swelling, and stiffness. This disease affects nearly 1% of the world population. RA predominates in females and typically develops between the ages of 30 and 50 years. Common therapeutics for the treatment of RA include immune system suppressants such as tumor necrosis factor, or TNF, inhibitors. There is growing concern related to multiple clinical cases reporting an unexpected onset of psoriasis following the use of TNF inhibitors. This adverse event is counterintuitive since some tumor necrosis factor inhibitors are indicated for the treatment of plaque psoriasis. In this study, we analyzed over 880 thousand postmarketing safety reports from patients being treated for RA with a single therapeutic and provided evidence for a statistically significant association of psoriasis adverse events with TNF inhibitor use as compared to methotrexate. Additionally, we quantified the reported odds ratios and their 95% confidence intervals between four individual TNF inhibitors and found that the degree of association with psoriasis was variable among the drugs studied, with certolizumab pegol exhibiting the highest reported risk. [ABSTRACT FROM AUTHOR]