Administration Of Certolizumab Pegol Research Articles

New-Onset, Treatment-Resistant Inflammatory Bowel Disease after Administration of Secukinumab for Plaque Psoriasis: A Case Report and Review of the Existing Literature.

Aberrant activation of the IL-23/IL-17 axis leads to inflammatory phenotypes with overlapping clinical characteristics. Inhibition of IL-17 has mostly an anti-inflammatory effect, but sporadic cases of new-onset IBD have been reported. We present the case of a 65-year-old male patient with new-onset Crohn's-like disease after treatment with secukinumab for skin psoriasis. Discontinuation of the IL-17 inhibitor and high-dose corticosteroid treatment were efficient initially, but a relapse was noted during corticosteroid tapering. Administration of certolizumab pegol did partially relieve the patient, but disease remission was only achieved with subcutaneous risankizumab therapy. Clinical trials and real-world data indicate sporadic cases of new-onset IBD in patients receiving IL-17 inhibitors. Interestingly, our case is a "treatment-resistant" one since treatment with a biologic disease-modifying drug (bDMARD) usually leads to disease remission. As such, it is crucial to investigate the special characteristics of this clinical entity.

Certolizumab pegol for maintenance of medically induced remission in Crohn'sdisease.

Crohn's disease (CD) is a disease with an impaired immune response characterized by chronic, relapsing-remitting, and progressive inflammation mainly affecting the gastrointestinal tract. Certolizumab pegol (CZP) is a biological agent that regulates the impaired immune response by controlling tumour necrosis factor-α (TNFα). However, the efficacy and safety of long-term administration of CZP for people with CD with inflammation under control are not well understood. To assess the efficacy and safety of CZP for maintenance of remission in people with CD. We searched CENTRAL, MEDLINE, Embase, ClinicalTrials.gov, WHO ICTRP, and conference abstracts from inception to 23 March 2022. We contacted pharmaceutical companies involved with the production of CZP for further relevant information. We included randomized controlled trials (RCTs) comparing CZP with placebo in adults with CD. Two review authors independently selected studies and extracted data. The main outcomes were failure to maintain clinical remission at week 26, failure to maintain clinical response at week 26, and serious adverse events. We planned to perform meta-analyses including all available studies if similar enough for pooling to be appropriate and calculated risk ratios (RRs) with 95% confidence intervals (CIs) for dichotomous outcomes and mean differences with 95% CIs for continuous outcomes. We analyzed the number needed to treat for an additional beneficial outcome (NNTB) and the number needed to treat for an additional harmful outcome (NNTH) to indicate the magnitude of treatment effects. The same two review authors independently evaluated the risk of bias by usingthe Cochrane RoB 2 tool and evaluated the certainty of evidence using the GRADE framework. We identified one study meeting our prespecified eligibility criteria. The included study enrolled 428adults with CD who responded to induction therapy with CZP 400 mg at weeks 0, 2, and 4. The study evaluated long-term efficacy and safety of CZP administered subcutaneously every four weeks compared with placebo. The proportion of participants who failed to maintain clinical remission at week 26 was 52.3% (113/216) in the CZP group compared to 71.7% (152/212) in the placebo group. Treatment of CZPprobably results in a large reduction in failure to maintain clinical remission at week 26 (RR 0.73, 95% CI 0.63 to 0.85). The NNTB was 5 (95% CI 4 to 9). We judged this outcome at low risk of bias. Using the GRADE assessment, we judged the certainty of evidence as moderate due to the low number of events occurred. The proportion of participants who failed to maintain clinical response at week 26 was 37.5% (81/216) in the CZP group compared to 64.2% (136/212) in the placebo group. Treatment of CZP probably results in a large reduction in failure to maintain clinical response at week 26 (RR 0.58, 95% CI 0.48 to 0.71). The NNTB was 4 (95% CI 3 to 5). We judged this outcome at low risk of bias. Using the GRADE assessment, we judged thecertainty of evidence as moderate due to the low number of events occurred. The proportion of participants who developed serious adverse events was 5.6% (12/216) in the CZP group compared to 6.6% (14/212) in the placebo group. Treatment of CZP maylead to no difference in serious adverse events compared to placebowhen used as a remission maintenance treatment (RR 0.84, 95% CI 0.40 to 1.78). The NNTB was 95 (95% CI NNTH 19 to NNTB 25). We evaluated the risk of bias for this outcome as low. We evaluated the certainty of evidence as low due tothe low number of events occurred and the CIs were not sufficiently narrow. CZP probably results in a large reduction in failure to maintain clinical remission and response at week 26 in people with CD. The evidence suggests that CZP may lead to no difference in serious adverse events compared to placebo when used as a remission maintenance treatment. However,the current studies are limited to 26 weeks of follow-up and only included adults. Therefore, these conclusions cannot be used to guide longer term treatment or for treatment in children at present.

Сравнительная эффективность генно-инженерных биологических препаратов в реальной клинической практике по данным МЕРА

Background: the list expansion of genetically engineered biological drugs (GEBD) used for the treatment of ankylosing spondylitis (AS) determines the relevance of studies aimed at comparing them and determining their place in this disease treatment. Real clinical practice studies are the preferred source of this data type. Aim: to evaluate the efficacy of various GEBD in patients with AS according to the Moscow Unified Arthritis Registry (MUAR). Material and methods: the analysis of the MUAR data was carried out. These included clinical cases with GEBD, for which there were data of a completed visit after 6 months or more after the treatment initiation. Parameters values achieved during treatment with various drugs were analyzed. The comparison was conducted during a multivariate analysis with adjustments for the identified confounders. Non-clinical parameters that were reliably and independently associated with the achieved BASDAI index (CRP) values were considered as confounders. Results: the study included 363 treatment episodes with GEBP in 361 patients. As mutually independent significant predictors of the achieved ASDAS (confounders) values, GEBD treatment duration were established until the evaluation of indicators (p<0.001) and the age of the patient (p=0.006). Significant association between the established values of the studied parameters and the used GEBD were found for the achieved ASDAS (p=0.033) and ESR (p=0.007) values. In a pairwise drug comparison using the conservative Šidák correction, the achieved values of ASDAS and ESR during infliximab and adalimumab administration were significantly less than during certolizumab pegol administration. Conclusion: infliximab, adalimumab, etanercept, certolizumab pegol, golimumab, secukinumab in real clinical practice demonstrate generally similar clinical efficacy in the treatment of AS. The effect of golimumab and secukinumab, recently introduced into clinical practice, does not significantly differ from the effect produced by long-term TNF-α inhibitors. Certain disease activity preservation in a significant part of patients gives grounds to continue the search for new treatment methods. KEYWORDS: ankylosing spondylitis, genetically engineered biological drugs, tumor necrosis factor inhibitors, C-reactive protein, confounders, registry. FOR CITATION: Rosochkina E.A., Lukina G.V., Koltsova E.N. et al. Comparative efficacy of genetically engineered biological drugs in real clinical practice according to the Moscow Unified Arthritis Registry (MUAR) data. Russian Medical Inquiry. 2021;5(2):58–63. DOI: 10.32364/2587-6821-2021-5-2-58-63.

Certolizumab pegol in the treatment of Takayasu arteritis.

Certolizumab pegol (CZP) is a PEGylated antigen-binding fragment-fragment of a humanized mAb neutralizing TNF. It lacks Fc-fragment and has a very low potential to cross the placenta. We aimed to report the efficacy and safety of CZP in a case series of patients with refractory Takayasu arteritis (TA). Ten females of reproductive age (18-35 years) with TA were treated with CZP (at a dose of 400 mg at weeks 0, 2 and 4 and at 200 mg every 2 weeks thereafter) for a median of 10 months (range 3-28). Prior to CZP administration all patients received glucocorticoids and ± MTX, CYC, AZA, HCQ, LEF or MMF. Six patients were previously treated with other biological anti-cytokine drugs. The National Institutes of Health criteria and the Indian Takayasu Clinical Activity Score 2010 were used to define disease activity. All patients rapidly responded to treatment with CZP and were able to taper prednisone and MTX doses. Treatment with CZP resulted in a significant decrease in median serum CRP levels and normalization of Indian Takayasu Clinical Activity Score 2010 score in 9 of 10 patients. Remission of systemic vasculitis was achieved in all patients. Seven patients maintained remission for at least 4 months, while one patient developed relapse after 2 years of CZP treatment. Side effects included mild infections (n = 5). Our case series suggests that CZP may be an effective and steroid-sparing treatment option in patients with active TA even if they did not previously respond to other TNF inhibitors or tocilizumab.

Long-term efficacy and safety of certolizumab pegol in Japanese rheumatoid arthritis patients with an inadequate response to methotrexate: 52-week results from an open-label extension of the J-RAPID study

Objectives. To evaluate the long-term efficacy and safety of certolizumab pegol (CZP) plus methotrexate treatment and to assess the efficacy of two CZP maintenance dosing schedules in Japanese rheumatoid arthritis (RA) patients with an inadequate response to methotrexate.Methods. J-RAPID double-blind patients were entered into an open-label extension (OLE) study. Patients withdrawn due to lack of efficacy at 16 weeks and double-blind completers without a week-24 American College of Rheumatology (ACR) 20 response received CZP 200 mg every other week (Q2W) plus methotrexate. Double-blind completers with week-24 ACR20 responses were randomized to CZP 200 mg Q2W plus methotrexate or CZP 400 mg every 4 weeks plus methotrexate.Results. The ACR20/ACR50/ACR70 response rates of double-blind completers (n = 204) were 89.7%/67.2%/36.3% at OLE entry and 95.6%/84.8%/58.3% at 52 weeks, respectively. Other clinical, functional and radiographic outcomes were sustained with long-term CZP plus methotrexate. Long-term treatment with CZP was well-tolerated with no new unexpected adverse events observed. The efficacy and safety of CZP treatment were similar between the two dosing schedules.Conclusions. Continued CZP administration with methotrexate maintained efficacy over 52 weeks and was well-tolerated for Japanese RA patients. No obvious differences in clinical efficacy and safety were observed between the two dosing schedules, giving flexibility in maintenance administration schedules.

Long-term efficacy and safety of certolizumab pegol in Japanese rheumatoid arthritis patients who could not receive methotrexate: 52-week results from an open-label extension of the HIKARI study

Objectives. To evaluate the long-term efficacy and safety of certolizumab pegol (CZP) treatment and to assess the efficacy of two CZP maintenance dosing schedules in Japanese rheumatoid arthritis (RA) patients who could not receive methotrexate (MTX).Methods. HIKARI double-blind (DB) patients were entered into an open-label extension (OLE) study. Patients withdrawn at 16 weeks due to lack of efficacy and DB completers without a 24-week American College of Rheumatology (ACR)20 response received CZP 200 mg every 2 weeks (Q2W). DB completers with 24-week ACR20 responses were randomized to CZP 200 mg Q2W or CZP 400 mg every 4 weeks.Results. The ACR20/ACR50/ACR70 response rates of DB completers (n = 98) were 82.7%/56.1%/34.7% at OLE entry, and 83.7%/65.3%/48.0% at 52 weeks, respectively. Other clinical, functional, and radiographic outcomes were sustained during long-term administration of CZP, even without MTX. No new unexpected adverse events were observed during long-term CZP treatment. The efficacy and safety of CZP treatment were similar between the two dosing schedules.Conclusions. Long-term CZP administration is efficacious and safe for RA patients. No obvious differences in clinical efficacy and safety were observed between the two dosing schedules. The choice between two maintenace regimens adds flexibility in administration schedules for RA patients and physicians.

Certolizumab pegol in therapy for rheumatoid arthritis

The paper reviews the literature on the new tumor necrosis factor-α (TNF-α) antagonist certolizumab pegol (CZP). It considers the experience in using the drug in Russia within the framework of the RAPID 2 trial. The currently obtained material suggests that CZP has extended the capacities of RA treatment. The drug may be successfully used both alone and in combination with other disease-modifying anti-rheumatic drugs and it is effective in all degrees of disease activity. The agent is noted for a particularly rapid achievement of its therapeutic effect, early exhibits antidestructive properties, and enables prediction of the long-term results of therapy at a relatively early stage of its use. It is improbable that the administration of CZP versus other TNF-α antagonists in pregnancy may be safer since it does not seem to penetrate the placental barrier. Emphasis is laid on the most convenient method for administration of the drug, namely, its subcutaneous route at large intervals. In this case there may be rare local reactions.

Therapie mit Certolizumab pegol bei Patienten mit destruierender Arthritis

Certolizumab pegol is a new anti-TNF-alpha inhibitor which has been approved for the treatment of rheumatoid arthritis since October 2009. Due to the modification of the antibody fragment by the adherence of polyethylene glycol (PEG) a sufficient distribution in inflammatory tissue was found in animal experiments. In two individual case reports a remission of therapy refractive arthritis was achieved by administration of certolizumab pegol.

A Cost-Efficacy Analysis Model for Physician Administered Anti-Tumor Necrosis Factor Agents in Crohnʼs Disease

Purpose: To provide a cost-efficacy (CE) analysis of achieving remission in Crohn's disease (CD) patients following treatment with infliximab or certolizumab pegol from a payer perspective. Methods: An Excel-based CE model was developed to estimate cost per successful remission of CD using published data for infliximab and certolizumab pegol. Dosing information was obtained from the product labels. Drug costs were obtained from First Databank data for April 2008 wholesale acquisition cost (WAC). The cost for one 100 mg vial of infliximab was $604, and for one 200 mg syringe of certolizumab pegol was $658. The medical cost for infliximab infusions was estimated to be $237 per infusion based on the Medicare 2005 infusion schedule. The medical cost per certolizumab pegol administration was estimated at $37 based on HCPCs code 99212, for an office outpatient visit. The cost of adverse events was not included in the model. Remission rates, defined as the percentage of patients achieving a Crohn's Disease Activity Index (CDAI) score of less than or equal to 150, were used as the efficacy measure. A remission rate of 39.0% was reported at week 30 in the ACCENT I trial for infliximab. A remission rate of 29.0% was reported at week 26 in the PRECISE I trial for certolizumab pegol. The time horizon on the study was 30 weeks, as long-term effectiveness data are not yet available for certolizumab pegol. Results: The average cost per successfully treated patient, those achieving remission based on the CDAI score was $33,922 for infliximab and $37,324 for certolizumab pegol. Conclusion: Based on this model, the cost of a successfully treated patient is higher for certolizumab pegol than infliximab, suggesting that infliximab is more cost effective than certolizumab pegol for treatment of CD. Direct comparative trials and real world data are needed to confirm these findings.

Determination of 40 kDa polyethylene glycol (PEG) excretion after subcutaneous administration of certolizumab pegol to rats

Determination of 40 kDa polyethylene glycol (PEG) excretion after subcutaneous administration of certolizumab pegol to rats

Measurement of the excretion of 40 kDa polyethylene glycol in urine following subcutaneous administration of certolizumab pegol in rats

Measurement of the excretion of 40 kDa polyethylene glycol in urine following subcutaneous administration of certolizumab pegol in rats

Certolizumab pegol in Crohn's disease

Certolizumab pegol is a humanized Fab' fragment monoclonal antibody to tumor necrosis factor alpha (TNF-alpha). PEGylation increases its half-life, and it is administered subcutaneously to treat immune-mediated inflammatory diseases such as Crohn's disease and rheumatoid arthritis. Certolizumab pegol improves quality of life and reduces clinical disease activity. Inflammatory markers such as C-reactive protein (CRP) also decrease after administration of certolizumab pegol. The dose for induction of remission is 400 mg subcutaneously at weeks 0, 2 and 4. The dose for maintenance of remission is 400 mg sc given every four weeks. The safety profile is comparable with other anti-TNF agents, and the major adverse events are related to infections. This article reviews the published data regarding the efficacy and safety of certolizumab pegol.

Determination of 40 kDa polyethylene glycol (PEG) excretion after subcutaneous administration of certolizumab pegol to rats

Determination of 40 kDa polyethylene glycol (PEG) excretion after subcutaneous administration of certolizumab pegol to rats

Measurement of Urinary Excretion of 40 kDa Polyethylene Glycol (PEG) after Subcutaneous Administration of Certolizumab Pegol in Rats

Measurement of Urinary Excretion of 40 kDa Polyethylene Glycol (PEG) after Subcutaneous Administration of Certolizumab Pegol in Rats