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 , Doenças Inflamatórias Intestinais , Fator de Necrose Tumoral alfa , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/patologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Anticorpos Monoclonais/uso terapêutico , Certolizumab Pegol/uso terapêutico , Adalimumab/uso terapêutico , Infliximab/uso terapêutico , Produtos Biológicos/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêuticoRESUMO
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
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
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
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
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: 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
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
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.
Assuntos
Anticorpos Monoclonais Humanizados , Antirreumáticos , Artrite Psoriásica , Interleucina-17 , Humanos , Artrite Psoriásica/tratamento farmacológico , Artrite Psoriásica/imunologia , Masculino , Feminino , Pessoa de Meia-Idade , Interleucina-17/antagonistas & inibidores , Interleucina-17/imunologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Adulto , Antirreumáticos/uso terapêutico , Adalimumab/uso terapêutico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Certolizumab Pegol/uso terapêutico , Idoso , Produtos Biológicos/uso terapêutico , Resultado do TratamentoRESUMO
INTRODUCTION: Crohn's disease (CD) is a chronic inflammatory bowel disease that can affect the entire gastrointestinal tract. The pathophysiology of CD includes a disrupted interplay of intestinal bacteria, the intestinal immune system and the intestinal surface in genetically susceptible individuals, which remains incompletely understood. Conventional therapies include steroids, but numerous advanced therapies are also available. Three tumor necrosis factor (TNF) inhibitors (infliximab, adalimumab and certolizumab pegol (Switzerland)) have been approved for MC. Additional treatment options include the interleukin (IL)-12/23 inhibitors ustekinumab and the integrin inhibitors vedolizumab. With risankizumab, a first selective IL-23 inhibitor for CD has been approved by the EMA in 2022. Moreover, the Janus kinase-1 inhibitor upadacitinib has been available for the treatment of CD in the EU since 2023. For localized CD, elective surgical resection also remains a valid option with good long-term outcomes. Perianal and fistulizing CD are difficult to treat and require a close interdisciplinary collaboration between gastroenterologists and colorectal surgeons. Surgical fistula treatment with curative intent should only be performed in well-controlled CD. The recent increase in therapeutic options in CD is encouraging, since more safe and effective therapies are now available to patients. Nevertheless, CD remains an incurable disease and so far, for all existing treatments only a fraction of patients responds to the therapy. Therefore, the development of new therapies should continue.
Assuntos
Doença de Crohn , Humanos , Doença de Crohn/diagnóstico , Doença de Crohn/tratamento farmacológico , Fator de Necrose Tumoral alfa/uso terapêutico , Infliximab/efeitos adversos , Certolizumab Pegol/efeitos adversos , Adalimumab/efeitos adversos , Resultado do TratamentoRESUMO
THE PURPOSE OF THE ARTICLE: Pyoderma gangrenosum (PG) is an ulcerating neutrophilic dermatosis with an incidence of 3-10 patients per million. PG equally affects patients of both sexes and of any age. Of these patients, 50-75% are associated with auto-immune disease. The lower extremities are the most commonly affected body parts. Minor trauma to the skin may result in the development of new lesions. Patients complain of chronic, nonhealing ulcers with associated pain. Treatment starts with systemic or intralesional corticosteroids, however, no official treatment protocol currently exists. Recent success has been found with biologic agents such as TNF-a inhibitor, although the treatment efficacy in these reports is limited. As for the pregnant patient, the drug selection is difficult. In this report, we want to assess the efficiency of certolizumab in the pregnant patient. RESULTS: We report a case of a patient with PG, who responded well to certolizumab, 400 mg as a booster dose, followed by 200 mg biweekly for 8 weeks. The lesions gradually resolved and followed up for 5months without side effect. In addition, we reviewed the literature and compared the current treatment efficiency in the treatment of PG. CONCLUSION: Certolizumab may be a promising therapeutic option for patients with severe PG.
Assuntos
Pioderma Gangrenoso , Masculino , Gravidez , Feminino , Humanos , Pioderma Gangrenoso/tratamento farmacológico , Pioderma Gangrenoso/patologia , Certolizumab Pegol/uso terapêutico , Pele/patologia , Corticosteroides/uso terapêutico , Resultado do Tratamento , Inibidores do Fator de Necrose Tumoral/uso terapêuticoRESUMO
PURPOSE: Nonresponse to an anti-tumor necrosis factor (TNF) agent in patients with Crohn disease (CD) is often managed by either a switch to a different class of biologic (ie, ustekinumab, vedolizumab) or by cycling to another anti-TNF agent (ie, adalimumab, infliximab, certolizumab pegol). Persistence after a switch to a different biologic class or after cycling within the anti-TNF class was assessed in patients with nonresponse to an anti-TNF agent. METHODS: Adults with CD who discontinued from an anti-TNF agent and either switched to a different class of biologic (ie, anti-interleukin/integrin; the switching cohort) or cycled within the anti-TNF class (the cycling cohort) between September 23, 2016, and August 1, 2019, were selected from a commercial database. The index date was defined as the date of the first claim of the subsequent-line biologic (index biologic) after an anti-TNF. The switching and cycling cohorts were balanced with regard to baseline characteristics, using inverse probability of treatment weights-average treatment effect (IPTW-ATE). Persistence with the index biologic was defined as consistent use with no gaps of >120 days (ustekinumab, vedolizumab, infliximab) or of >60 days (adalimumab, certolizumab pegol) in biologic supply. Composite end points were persistence while being corticosteroid-free (defined as no use of corticosteroids with ≥14 days of supply after day 90 post-index) and persistence while on monotherapy (no immunomodulators/nonindex biologics). Weighted Kaplan-Meier and Cox models were used to assess outcomes at 12 months post-index. FINDINGS: There were 444 patients in the weighted switching cohort (mean age, 40.4 years; 56.3% female) and 441 in the weighted cycling cohort (mean age, 39.5 years; 58.4% female). At 12 months post-index, the rate of persistence with the index biologic was 75.7% in the switching cohort compared to 67.5% in the cycling cohort (log-rank P = 0.023); the rate of persistence while on monotherapy was 58.2% compared to 44.2%, respectively (log-rank P < 0.001). The rate of persistence was 44% greater in the switching compared to that in the cycling cohort (hazard ratio [HR] = 1.44; 95% CI, 1.11-1.88; P = 0.007); the rate of persistence while on monotherapy was 56% greater in the switching cohort (HR = 1.56; 95% CI, 1.28-1.90; P < 0.001). The between-cohort difference in persistence while being corticosteroid-free was not statistically significant (HR = 1.08; 95% CI, 0.89-1.32; P = 0.426). IMPLICATIONS: Patients with CD who switched to a different biologic class were more persistent than were patients who cycled to another anti-TNF agent. These findings may be useful for physicians when considering the treatment of patients who have experienced nonresponse or loss of response to the first-line anti-TNF agent.
Assuntos
Doença de Crohn , Adulto , Humanos , Feminino , Masculino , Doença de Crohn/tratamento farmacológico , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Infliximab/uso terapêutico , Adalimumab/uso terapêutico , Fatores Biológicos , Certolizumab Pegol/uso terapêutico , Ustekinumab , Estudos Retrospectivos , Fator de Necrose Tumoral alfa , Necrose/induzido quimicamenteRESUMO
Anti-tumour necrosis factor (TNF)-α agents have been increasingly used to treat patients affected by inflammatory bowel disease and dermatological and rheumatologic inflammatory disorders. However, the widening use of biologics is related to a new class of adverse events called paradoxical reactions. Its pathogenesis remains unclear, but it is suggested that cytokine remodulation in predisposed individuals can lead to the inflammatory process. Here, we dissect the clinical aspects and overall outcomes of autoimmune diseases caused by anti-TNF-α therapies.
Assuntos
Doenças Autoimunes , Doenças Inflamatórias Intestinais , Humanos , Adalimumab/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Certolizumab Pegol/uso terapêutico , Etanercepte/uso terapêutico , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Fator de Necrose Tumoral alfa/uso terapêutico , Doenças Autoimunes/tratamento farmacológico , Doenças Autoimunes/induzido quimicamente , Doenças Inflamatórias Intestinais/etiologia , Doenças Inflamatórias Intestinais/induzido quimicamente , Necrose/tratamento farmacológico , Infliximab/uso terapêuticoRESUMO
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.
Assuntos
Antirreumáticos , Artrite Reumatoide , Humanos , Antirreumáticos/efeitos adversos , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/tratamento farmacológico , Certolizumab Pegol/efeitos adversos , Método Duplo-Cego , Quimioterapia Combinada , Metotrexato/efeitos adversos , Fator Reumatoide , Resultado do Tratamento , Inibidores do Fator de Necrose Tumoral/uso terapêuticoRESUMO
BACKGROUND: We previously analyzed data from blood examination screenings, including serum Krebs von den Lungen (KL) -6 level, before starting biologic treatment for psoriasis in a real-world setting. However, we did not follow change in KL-6 level after the initiation of biologics. Furthermore, there has been no follow-up study of certolizumab pegol, risankizumab, or tildrakizumab. This study evaluated change in serum KL-6 levels in patients during treatment with biologics, including certolizumab pegol, risankizumab, and tildrakizumab. METHODS: We analyzed data from 111 patients. Change in KL-6 level was regarded as significant if it increased to greater than 500 U/mL at least once and if the maximum level after treatment with biologics was at least 1.5 times that of the baseline level. RESULTS: KL-6 level significantly changed during treatment with TNF inhibitors, IL-17 inhibitors, and IL-23 inhibitors in 9 (20.9%), 2 (6.3%), and 2 (5.6%) patients, respectively. Mean age, mean baseline KL-6 level, and frequency of TNF inhibitor use were higher in patients with a significant change in KL-6 level than those in patients without a significant change. Ten patients had minor interstitial changes on chest CT scans but no clinical signs suggesting interstitial pneumonia. CONCLUSIONS: Older patients with psoriasis and high baseline KL-6 levels must be carefully monitored during treatment with biologics, especially TNF inhibitors. Monitoring of KL-6 level and chest CT scans is necessary to exclude the possibility of drug-induced interstitial pneumonia.
Assuntos
Produtos Biológicos , Doenças Pulmonares Intersticiais , Psoríase , Humanos , Certolizumab Pegol/uso terapêutico , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Doenças Pulmonares Intersticiais/diagnóstico , Psoríase/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Mucina-1/uso terapêutico , BiomarcadoresRESUMO
BACKGROUND: We previously evaluated blood screening data, including antinuclear antibodies (ANA), before initiating biologic treatment for patients with psoriasis in a real-world setting. However, we did not analyze change in ANA titers after the start of biologics. No previous study has comprehensively investigated change in ANA titers over time in individual patients or the effectiveness of certolizumab pegol or tildrakizumab. OBJECTIVES: This study evaluated change in ANA titers in individual patients during treatment with biologics, including certolizumab pegol and tildrakizumab. METHODS: 111 patients were included in this study. Change in ANA was regarded as significant when the ANA titer was ×80 or more in patients with a previously undetectable ANA titer or when it increased by fourfold or more in those with a detectable ANA titer before treatment. RESULTS: The ratios of patients with a significant change in ANA titer who were treated with a tumor necrosis factor (TNF) inhibitor, interleukin (IL) -17 inhibitor, or IL-23 inhibitor were 34.9% (15/43), 0.0% (0/32), and 0.0% (0/36), respectively. There were 4 patterns of significant change in ANA titer: (i) an increase (n=8), (ii) a decrease after an increase (n=4), (iii) a decrease after an increase with a drug change (n=2), and (iv) an increase after a decrease after an increase (n=1). No symptom suggesting lupus syndrome was noted. CONCLUSIONS: ANA titers must be carefully monitored throughout treatment with biologics, especially TNF inhibitors, and the possibility of lupus-like syndrome should be excluded.
Assuntos
Produtos Biológicos , Psoríase , Humanos , Anticorpos Monoclonais/efeitos adversos , Anticorpos Antinucleares , Certolizumab Pegol , Psoríase/tratamento farmacológicoRESUMO
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.