RESUMO
Inflammatory bowel disease (IBD), which includes ulcerative colitis and Crohn's disease, is a chronic condition characterized by relapsing and remitting inflammation of the gastrointestinal tract. The pathogenesis involves a complex interplay of genetic, environmental, and immune factors. Treatment paradigms have evolved significantly over the past few decades, with the introduction of biologics, particularly anti-TNF (tumor necrosis factor) agents, marking a significant advancement. Anti-TNF therapies, including infliximab, adalimumab, golimumab, and certolizumab pegol, have efficacy in inducing and maintaining remission, promoting mucosal healing, and improving the quality of life in moderate to severe IBD patients. The early and appropriate use of these agents can mitigate disease progression and reduce the dependency on corticosteroids, enhancing long-term patient outcomes. Nevertheless, these therapies are expensive and are associated with potential adverse effects, including increased risk of infections and malignancies. This review discusses the mechanisms, clinical efficacy, safety profiles, and therapeutic positioning of anti-TNF agents in IBD management, integrating current Korean treatment guidelines.
Assuntos
Anticorpos Monoclonais Humanizados , Produtos Biológicos , Doenças Inflamatórias Intestinais , Fator de Necrose Tumoral alfa , Humanos , Adalimumab/uso terapêutico , Anticorpos Monoclonais Humanizados/farmacologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Certolizumab Pegol/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/patologia , Infliximab/uso terapêutico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/metabolismoRESUMO
OBJECTIVE: It was targeted to assess the efficacy of certolizumab on pancreas and target organs via biochemical parameters and histopathologic scores in experimental acute pancreatitis (AP). MATERIALS AND METHODS: Forty male Sprague Dawley rats were divided into the following 5 equal groups: group 1 (sham group), group 2 (AP group), group 3 (AP + low-dose certolizumab group), group 4 (AP + high-dose certolizumab group), and group 5 (placebo group). Rats in all groups were sacrificed 24 hours after the last injection and amylase, tumor necrosis factor α, transforming growth factor ß, interleukin 1ß, malondialdehyde, superoxide dismutase, and glutathione peroxidase levels were studied in blood samples. Histopathological investigation of both the pancreas and target organs (lungs, liver, heart, kidneys) was performed by a pathologist blind to the groups. In silico analysis were also accomplished. RESULTS: The biochemical results in the certolizumab treatment groups were identified to be significantly favorable compared to the AP group (P < 0.001). The difference between the high-dose group (group 4) and low-dose treatment group (group 3) was found to be significant in terms of biochemical parameters and histopathological scores (P < 0.001). In terms of the effect of certolizumab treatment on the target organs (especially on lung tissue), the differences between the low-dose treatment group (group 3) and high-dose treatment group (group 4) with the AP group (group 2) were significant. CONCLUSIONS: Certolizumab has favorable protective effects on pancreas and target organs in AP. It may be a beneficial agent for AP treatment and may prevent target organ damage.
Assuntos
Amilases , Pulmão , Pâncreas , Pancreatite , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa , Animais , Masculino , Pancreatite/prevenção & controle , Pancreatite/induzido quimicamente , Pancreatite/patologia , Pancreatite/tratamento farmacológico , Pâncreas/efeitos dos fármacos , Pâncreas/patologia , Pâncreas/metabolismo , Amilases/sangue , Doença Aguda , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Fator de Necrose Tumoral alfa/sangue , Certolizumab Pegol/farmacologia , Malondialdeído/metabolismo , Fígado/efeitos dos fármacos , Fígado/patologia , Fígado/metabolismo , Rim/efeitos dos fármacos , Rim/patologia , Rim/metabolismo , Interleucina-1beta/sangue , Interleucina-1beta/metabolismo , Superóxido Dismutase/metabolismo , Glutationa Peroxidase/metabolismo , Miocárdio/patologia , Miocárdio/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Ratos , Modelos Animais de Doenças , Estresse Oxidativo/efeitos dos fármacosRESUMO
The neuroinflammatory response triggered by cerebral ischemia-reperfusion injury (CIRI) is characterized by the upsurge of pro-inflammatory cytokines, including TNF-α, IL-1ß, and IL-6, which promote leukocyte infiltration and subsequent accumulation in the ischemic zone. This accumulation further intensifies inflammation and aggravates ischemic damage. Certolizumab pegol (CZP), a monoclonal antibody targeting TNF-α, is widely used in treating various inflammatory diseases. This study explored the therapeutic potential of CZP in a mouse model of CIRI, induced by middle cerebral artery occlusion (MCAO), focusing on its influence on the microglial inflammatory response. In vitro analyses revealed that CZP markedly inhibits TNF-α-stimulated inflammation in primary microglia with an EC50 of 1.743 ng/mL. In vivo, MCAO mice treated with CZP (10 µg/mouse, i.p.) for 3 days showed reduced infarct volume, partially improved neurological function, and diminished blood-brain barrierdisruption. Additionally, CZP treatment curtailed microglial activation and the release of pro-inflammatory mediators in the early stages of stroke. It also favorably modulated microglial M1/M2 polarization, rebalanced Th17/Treg cells dynamics, and inhibited Caspase-8-mediated GSDMD cleavage, preventing microglial pyroptosis. Collectively, this study described that the treatment with CZP reversed damaging process caused by CIRI, offering a promising therapeutic strategy for the treatment of ischemic stroke.
Assuntos
Certolizumab Pegol , Infarto da Artéria Cerebral Média , Camundongos Endogâmicos C57BL , Microglia , Traumatismo por Reperfusão , Fator de Necrose Tumoral alfa , Animais , Traumatismo por Reperfusão/tratamento farmacológico , Certolizumab Pegol/uso terapêutico , Certolizumab Pegol/farmacologia , Masculino , Camundongos , Microglia/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo , Infarto da Artéria Cerebral Média/tratamento farmacológico , Modelos Animais de Doenças , Isquemia Encefálica/tratamento farmacológico , Células Cultivadas , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/farmacologia , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/metabolismo , Humanos , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Encéfalo/metabolismo , Citocinas/metabolismoRESUMO
OBJECTIVE: There is a paucity of data on long-term clinical responses in patients with non-radiographic axial spondyloarthritis (nr-axSpA) based on their baseline objective signs of inflammation such as MRI or C-reactive protein (CRP) levels. This study reports clinical outcomes up to 3 years of the C-axSpAnd trial, including safety follow-up extension (SFE) from Weeks 52 to 156, stratified by patients' baseline MRI and CRP status. METHODS: C-axSpAnd (NCT02552212) was a phase 3, multicentre study that evaluated certolizumab pegol (CZP) in patients with active nr-axSpA who had active sacroiliitis on MRI and/or elevated CRP. In this post hoc analysis, efficacy outcomes are reported to Week 156 of C-axSpAnd for patients stratified according to their MRI and CRP status at Week 0 (MRI+/CRP-, MRI-/CRP+ and MRI+/CRP+). RESULTS: Across all outcome measures, including major improvement in Ankylosing Spondylitis Disease Activity Score (ASDAS-MI) and Assessment of SpondyloArthritis international Society criteria ≥40% response (ASAS40), outcomes were generally sustained in SFE patients from Week 52 to Week 156. MRI+/CRP+ patients showed numerically higher or comparable responses relative to MRI-/CRP+ and MRI+/CRP- patients at Weeks 52 and 156; however, all three subgroups demonstrated substantial improvements from Week 0 (in CZP-randomised patients, ASDAS-MI at Week 156 [observed case]: MRI+/CRP+: 73.1%, MRI-/CRP+: 52.2%, MRI+/CRP-: 30.4%; ASAS40: MRI+/CRP+: 76.9%, MRI-/CRP+: 62.5%, MRI+/CRP-: 65.2%). CONCLUSIONS: In patients with nr-axSpA and objective signs of inflammation, long-term clinical outcomes achieved after 1 year were generally sustained at 3 years across MRI+/CRP+, MRI-/CRP+ and MRI+/CRP- subgroups.
Assuntos
Espondiloartrite Axial , Proteína C-Reativa , Certolizumab Pegol , Imageamento por Ressonância Magnética , Humanos , Certolizumab Pegol/uso terapêutico , Proteína C-Reativa/análise , Proteína C-Reativa/metabolismo , Masculino , Feminino , Adulto , Resultado do Tratamento , Espondiloartrite Axial/tratamento farmacológico , Espondiloartrite Axial/etiologia , Pessoa de Meia-Idade , Biomarcadores , Índice de Gravidade de DoençaRESUMO
Biologic therapies targeting tumor necrosis factor alpha (TNF-α) (infliximab, adalimumab, certolizumab, etanercept), the p40 subunit shared by IL-12 and IL-23 (ustekinumab), the p19 subunit of IL-23 (guselkumab, tildrakizumab, risankizumab), IL-17A (secukinumab, ixekizumab), IL-17-RA (brodalumab) and both IL-17A and IL-17F (bimekizumab) have revolutionized the treatment of psoriasis. In both the short and long term, risankizumab had highest Psoriasis Area and Severity Index 90 scores compared to other oral and injectable biologics. IL-23 inhibitors had lowest rates of short-term and long-term adverse events and most favorable long-term risk-benefit profile compared to IL-17, IL-12/23, and TNF-α inhibitors.
Assuntos
Anticorpos Monoclonais Humanizados , Anticorpos Monoclonais , Produtos Biológicos , Psoríase , Ustekinumab , Psoríase/tratamento farmacológico , Humanos , Produtos Biológicos/uso terapêutico , Ustekinumab/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Etanercepte/uso terapêutico , Adalimumab/uso terapêutico , Infliximab/uso terapêutico , Interleucina-17/antagonistas & inibidores , Fármacos Dermatológicos/uso terapêutico , Certolizumab Pegol/uso terapêutico , Interleucina-23/antagonistas & inibidores , Interleucina-12/antagonistas & inibidoresRESUMO
Pediatric psoriasis is a chronic inflammatory skin condition. Current treatment modalities include topical medications, phototherapy, and systemic drugs, including biological agents. In cases of moderate-to-severe psoriasis recalcitrant to other therapies, biological therapies are often an attractive option given their dosing schedules, safety profiles, and need for less frequent laboratory monitoring, when compared with traditional systemic therapies. This article reviews biological treatment options approved for pediatric psoriasis and identifies others actively under investigation.
Assuntos
Adalimumab , Produtos Biológicos , Fármacos Dermatológicos , Psoríase , Ustekinumab , Humanos , Psoríase/tratamento farmacológico , Psoríase/terapia , Criança , Adalimumab/uso terapêutico , Produtos Biológicos/uso terapêutico , Ustekinumab/uso terapêutico , Fármacos Dermatológicos/uso terapêutico , Terapia Biológica , Infliximab/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Etanercepte/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Rituximab/uso terapêutico , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Alefacept , Certolizumab Pegol/uso terapêuticoRESUMO
BACKGROUND: Psoriatic arthritis (PA) is a chronic inflammatory systemic arthritis that can result in loss of functional capacity and joint deformation. This systematic review assessed the effectiveness and safety of biological and target synthetic drugs for treating PA. METHODS: We searched for randomized clinical trials (RCTs) that evaluated the use of Adalimumab, Etanercept, Infliximab, Golimumab, Secukinumab, Certolizumab Pegol and Tofacitinib in the main general databases and clinical trial registers databases. The primary outcomes were ACR 50, PsARC, and serious adverse events. Two independent reviewers performed study selection and data extraction. Network meta-analyses were conducted using a random effects model and frequentist approach. The CINeMA software was used to assess the certainty of evidence. RESULTS: We included 33 RCTs (n = 11,034). The results from the network meta-analysis for the ACR 50 at 6-months follow-up showed that all drugs were superior to placebo, with Secukinumab (high certainty of evidence), Infliximab (very low certainty of evidence) and Adalimumab (high certainty of evidence) ranking the highest. Regarding the PsARC (at 6-months follow-up), all drugs, except for Golimumab (very low certainty of evidence), were superior to placebo, with Etanercept (low certainty of evidence), Infliximab (low certainty of evidence) and Certolizumab Pegol (low certainty of evidence) being the most effective drugs. There were no significant differences in the risk of serious adverse events between the drugs and placebo. Golimumab (very low certainty of evidence), Secukinumab (low certainty of evidence), and Adalimumab (very low certainty of evidence) ranked the highest for safety. CONCLUSIONS: In conclusion, based on the balance between efficacy and safety, Secukinumab and Adalimumab may be the preferred options among the evaluated drugs for treating patients with PsA. However, caution is necessary when interpreting the safety findings, as they are supported by evidence of low to very low certainty. Consequently, the balance between benefits and potential risks may change as new safety evaluation studies become available. PROTOCOL REGISTRATION: PROSPERO: CRD42022315577.
Assuntos
Antirreumáticos , Artrite Psoriásica , Produtos Biológicos , Medicamentos Sintéticos , Humanos , Adalimumab/efeitos adversos , Adalimumab/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Antirreumáticos/uso terapêutico , Antirreumáticos/efeitos adversos , Artrite Psoriásica/tratamento farmacológico , Produtos Biológicos/efeitos adversos , Produtos Biológicos/uso terapêutico , Certolizumab Pegol/efeitos adversos , Certolizumab Pegol/uso terapêutico , Etanercepte/efeitos adversos , Etanercepte/uso terapêutico , Fragmentos Fab das Imunoglobulinas/uso terapêutico , Fragmentos Fab das Imunoglobulinas/efeitos adversos , Infliximab/efeitos adversos , Infliximab/uso terapêutico , Metanálise em Rede , Piperidinas/uso terapêutico , Piperidinas/efeitos adversos , Pirimidinas/uso terapêutico , Pirimidinas/efeitos adversos , Pirróis/uso terapêutico , Pirróis/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Medicamentos Sintéticos/efeitos adversos , Medicamentos Sintéticos/uso terapêutico , Resultado do TratamentoRESUMO
BACKGROUND: Disease-modifying antirheumatic drugs (DMARDs) are widely used for treating rheumatoid arthritis (RA). However, there are no established biomarkers to predict a patient's response to these therapies. Prostanoids, encompassing prostaglandins, prostacyclins, and thromboxanes, are potent lipid mediators implicated in RA progression. Nevertheless, the influence of DMARDs on prostanoid biosynthesis in RA patients remains poorly understood. This study aims to assess the impact of various DMARDs on urinary prostanoids levels and to explore whether urinary prostanoid profiles correlate with disease activity or response to therapy. METHODS: This study included 152 Swedish female patients with early RA, all rheumatoid factor (RF) positive, enrolled in the NORD-STAR trial (registration number: NCT01491815). Participants were randomized into four therapeutic regimes: methotrexate (MTX) combined with (i) prednisolone (arm ACT), (ii) TNF-α blocker certolizumab pegol (arm CZP), (iii) CTLA-4Ig abatacept (arm ABA), or (iv) IL-6R blocker tocilizumab (arm TCZ). Urine samples, collected before start of treatment and at 24 weeks post-treatment, were analyzed for tetranor-prostaglandin E metabolite (tPGEM), tetranor-prostaglandin D metabolite (tPGDM), 2,3-dinor thromboxane B2 (TXBM), 2,3-dinor-6-keto prostaglandin F1a (PGIM), leukotriene E4 (LTE4) and 12-hydroxyeicosatetraenoic acid (12-HETE) using liquid chromatography-mass spectrometry (LC-MS). Generalized estimating equation (GEE) models were used to analyze the change in urinary eicosanoids and their correlations to clinical outcomes. RESULTS: Patients receiving MTX combined with CZP or TCZ exhibited significant elevations in urinary tPGEM and TXBM levels after 24 weeks of treatment. Other eicosanoids did not show significant alterations in response to any treatment. Baseline urinary eicosanoid levels did not correlate with baseline clinical disease activity index (CDAI) levels, nor with changes in CDAI from baseline to week 24. Their levels were also similar between patients who achieved CDAI remission and those with active disease at week 24. CONCLUSIONS: Treatment with anti-TNF or anti-IL6R agents in early RA patients leads to an increased systemic production of proinflammatory and prothrombotic prostanoids. However, urinary eicosanoid levels do not appear to be predictive of the response to DMARDs therapy.
Assuntos
Antirreumáticos , Artrite Reumatoide , Dimaprit/análogos & derivados , Humanos , Feminino , Prostaglandinas , Antirreumáticos/uso terapêutico , Inibidores do Fator de Necrose Tumoral , Artrite Reumatoide/tratamento farmacológico , Metotrexato , Certolizumab PegolRESUMO
Psoriasis pathogenesis involves TNF-α, IL-23 and IL17, against which biologics have been highly effective. Among the five TNF-α inhibitors available for psoriasis, namely infliximab, adalimumab, etanercept, golimumab and certolizumab pegol (CZP), CZP has a unique mechanism of action due to its structure. As CZP lacks the Fc region, it does not cross the placenta and can be safely used in pregnant women. Its PEGylated nature allows for longer distribution time in tissues, potentially leading to a longer-lasting effect compared with other TNF-α inhibitors. In clinical trials, the efficacy of CZP on psoriasis skin symptoms and joint symptoms was comparable to other TNF-α inhibitors, with no discernible differences in safety profiles.
Psoriasis is a skin condition that affects the skin and causes joint problems. There are some medicines called TNF-α inhibitors that work well, especially for the joint issues. There are currently five TNF-α inhibitors available for treating psoriasis. One of these, certolizumab pegol, is different from the others. It lacks a specific part, which makes it less likely to pass through the placenta. This means it's safer for pregnant and breastfeeding women. Clinical trials have shown that certolizumab pegol is just as effective as other TNF-α inhibitors for treating the skin and joint symptoms of psoriasis. It's also equally safe.
Assuntos
Psoríase , Fator de Necrose Tumoral alfa , Humanos , Feminino , Gravidez , Certolizumab Pegol/uso terapêutico , Psoríase/tratamento farmacológico , Adalimumab/uso terapêutico , Infliximab/uso terapêutico , Resultado do TratamentoRESUMO
OBJECTIVE: To assess whether the retention rate of certolizumab pegol (CZP) was longer than that of other tumour necrosis factor inhibitors (TNFi) based on baseline rheumatoid factor (RF) levels. METHODS: Longitudinal, retrospective and multicentre study including patients with RA who were treated with any TNFi (monoclonal antibodies (mAB), etanercept (ETA) or CZP). Log-rank test and Cox regressions were conducted to evaluate the retention rate in the three groups according to the level of RF, with the third quartile of the baseline levels used as cut-off: <200 (Assuntos
Artrite Reumatoide
, Inibidores do Fator de Necrose Tumoral
, Humanos
, Estudos Retrospectivos
, Inibidores do Fator de Necrose Tumoral/uso terapêutico
, Fator Reumatoide
, Resultado do Tratamento
, Artrite Reumatoide/tratamento farmacológico
, Certolizumab Pegol/uso terapêutico
, Etanercepte/uso terapêutico
, Anticorpos Monoclonais/uso terapêutico
RESUMO
OBJECTIVES: Machine learning models can support an individualized approach in the choice of bDMARDs. We developed prediction models for 5 different bDMARDs using machine learning methods based on patient data derived from the Austrian Biologics Registry (BioReg). METHODS: Data from 1397 patients and 19 variables with at least 100 treat-to-target (t2t) courses per drug were derived from the BioReg biologics registry. Different machine learning algorithms were trained to predict the risk of ineffectiveness for each bDMARD within the first 26 weeks. Cross-validation and hyperparameter optimization were applied to generate the best models. Model quality was assessed by area under the receiver operating characteristic (AUROC). Using explainable AI (XAI), risk-reducing and risk-increasing factors were extracted. RESULTS: The best models per drug achieved an AUROC score of the following: abatacept, 0.66 (95% CI, 0.54-0.78); adalimumab, 0.70 (95% CI, 0.68-0.74); certolizumab, 0.84 (95% CI, 0.79-0.89); etanercept, 0.68 (95% CI, 0.55-0.87); tocilizumab, 0.72 (95% CI, 0.69-0.77). The most risk-increasing variables were visual analytic scores (VAS) for abatacept and etanercept and co-therapy with glucocorticoids for adalimumab. Dosage was the most important variable for certolizumab and associated with a lower risk of non-response. Some variables, such as gender and rheumatoid factor (RF), showed opposite impacts depending on the bDMARD. CONCLUSION: Ineffectiveness of biological drugs could be predicted with promising accuracy. Interestingly, individual parameters were found to be associated with drug responses in different directions, indicating highly complex interactions. Machine learning can be of help in the decision-process by disentangling these relations.
Assuntos
Antirreumáticos , Artrite Reumatoide , Produtos Biológicos , Humanos , Antirreumáticos/uso terapêutico , Etanercepte/uso terapêutico , Adalimumab/uso terapêutico , Abatacepte/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Áustria , Produtos Biológicos/uso terapêutico , Certolizumab Pegol/uso terapêutico , Sistema de Registros , Inteligência ArtificialAssuntos
Certolizumab Pegol , Dessensibilização Imunológica , Hipersensibilidade a Drogas , Humanos , Certolizumab Pegol/efeitos adversos , Certolizumab Pegol/uso terapêutico , Dessensibilização Imunológica/métodos , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/imunologia , Injeções Subcutâneas , Feminino , Masculino , Pessoa de Meia-IdadeRESUMO
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.
Assuntos
Antirreumáticos , Espondiloartrite Axial , Espondilartrite , Feminino , Humanos , Masculino , Adalimumab/uso terapêutico , Antirreumáticos/uso terapêutico , Certolizumab Pegol/uso terapêutico , Etanercepte/uso terapêutico , França , Espondilartrite/tratamento farmacológico , Resultado do Tratamento , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Fator de Necrose Tumoral alfa/uso terapêutico , Estudos RetrospectivosRESUMO
OBJECTIVES: Certolizumab pegol (CZP), an Fc-free antibody fragment, has shown stable serum levels and steady efficacy in the treatment of RA patients, irrespective of RF levels at baseline. Here, we examine, in clinical practice, the effect of baseline RF and ACPA levels on serum drug levels of IFX, ADL and CZP an Fc-free antibody fragment. METHODS: This is a retrospective study performed in real-world patients. We assessed 170 patients with RA: 90 (53%) received IFX, 48 (28%) ADL and 32 (19%) CZP. Demographic and clinical variables, RF and ACPA levels were obtained at the baseline visit (T0), and patients were stratified based on negative, low, medium, or high levels. After 6 months (T6) serum drug levels and anti-drug antibodies (ADAb), were computed. RESULTS: While CZP serum levels did not differ across RF groups at T6, high baseline RF was linked to lower serum drug levels compared to RF negative status in treatment with complete monoclonal antibodies IFX and ADL. No differences in disease activity measured by DAS28 at baseline were observed across RF quartiles in patients treated with IFX or ADL. ADAb was observed in 26 patients with IFX, 3 with ADL and 1 with CZP, following 6 months of treatment. Patients with high baseline RF levels dropped out more frequently by secondary non-response in IFX or ADL than CZP (80% vs. 75% vs. 33%, p=0.002). CONCLUSIONS: In this real word data evaluation, CZP serum levels were independent of RF levels in patients however patients with high baseline RF levels who obtained IFX or ADL had lower serum drug levels at 6 months than baseline RF-negative patients. In addition, secondary non-response was more frequent in patients with high RF levels treated with IFX and ADL.
Assuntos
Antirreumáticos , Artrite Reumatoide , Certolizumab Pegol , Fator Reumatoide , Humanos , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/sangue , Artrite Reumatoide/imunologia , Artrite Reumatoide/diagnóstico , Feminino , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fator Reumatoide/sangue , Certolizumab Pegol/uso terapêutico , Certolizumab Pegol/sangue , Idoso , Antirreumáticos/uso terapêutico , Antirreumáticos/sangue , Resultado do Tratamento , Anticorpos Antiproteína Citrulinada/sangue , Adulto , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Inibidores do Fator de Necrose Tumoral/sangue , Infliximab/sangue , Infliximab/uso terapêutico , Infliximab/imunologia , Monitoramento de Medicamentos/métodos , Biomarcadores/sangue , Fatores de TempoRESUMO
OBJECTIVE: To provide evidence of the effectiveness of certolizumab pegol (CZP) in real clinical practice in adult patients with moderate-to-severe plaque psoriasis (PsO) in the context of a risk-sharing agreement (RSA). METHODS: Retrospective observational study based on variables collected in the RSA for treatment with CZP of adult patients with moderate-severe plaque PsO. Ten Spanish hospitals where the RSA was implemented participated. The percentage of patients who achieved the target clinical response of the RSA at the follow-up visit (week 16) was evaluated: absolute Psoriasis Area and Severity Index (PASI) value ≤3 for biologic naïve population, and ≤5 in case of previous failure to a single biologic drug. In addition, the improvement in the scores of other scales included in the study was analyzed: Body Surface Area (BSA), Dermatology Life Quality Index (DLQI), Physician's Global Assessment (PGA), and Nail Psoriasis Severity Index (NAPSI). A descriptive analysis was performed for the total population and by patient subgroups (naive vs. non-naive to biologic, male vs. female, and with vs. without discontinuation). RESULTS: Sixty-six patients were included, 12 men and 54 women. 90.9% achieved the target clinical response, with a mean reduction of 8 (-78.4%) absolute PASI points. Improvement was observed in BSA, PGA, NAPSI and DLQI, with a reduction of 11.3 (-80.6%), 1.9 (-65.5%), 3.3 (-30.7%) and 9.0 (-66.4%) absolute value points, respectively. Despite not achieving the therapeutic target set in the RSA in six patients (9%) (the cost of the drug was assumed by the laboratory), only two (3%) discontinued treatment. CONCLUSION: Our study shows that CZP is effective in real clinical practice in patients with moderate-severe plaque PsO, with an improvement in absolute PASI and DLQI, as well as other scales, both for the total population and in the subgroups analyzed. Nearly 91% of patients reached the therapeutic target fixed in the RSA. Implementing this type of agreement can provide a direct or indirect benefit for all the agents involved in the process, providing valuable information for decision-making.
Assuntos
Produtos Biológicos , Psoríase , Adulto , Feminino , Humanos , Masculino , Certolizumab Pegol/uso terapêutico , Resultado do Tratamento , Psoríase/tratamento farmacológico , Psoríase/induzido quimicamente , Produtos Biológicos/uso terapêutico , Índice de Gravidade de Doença , Qualidade de VidaRESUMO
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 (ß -4.65, 95% CI -5.83 to -3.46; P < 0.001) or abatacept (ß -1.15, 95% CI -2.27 to -0.03; P = 0.04), and it was numerically lower in combination with certolizumab-pegol (ß -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.
Assuntos
Antirreumáticos , Artrite Reumatoide , Humanos , Metotrexato/uso terapêutico , Antirreumáticos/efeitos adversos , Abatacepte/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/induzido quimicamente , Certolizumab Pegol/uso terapêutico , Quimioterapia Combinada , Resultado do TratamentoRESUMO
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.
Assuntos
Antirreumáticos , Artrite Reumatoide , Humanos , Certolizumab Pegol/farmacocinética , Certolizumab Pegol/uso terapêutico , Anticorpos , Artrite Reumatoide/tratamento farmacológico , Algoritmos , Antirreumáticos/uso terapêuticoRESUMO
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.
Assuntos
Transtornos da Pigmentação , Púrpura , Humanos , Certolizumab Pegol/efeitos adversos , Fator de Necrose Tumoral alfa , Pele/patologia , Púrpura/induzido quimicamente , Púrpura/diagnóstico , Púrpura/complicaçõesRESUMO
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.