The effect of certolizumab drug concentration and anti-drug antibodies on TNF neutralisation

Berkhout, Lea C.; Vogelzang, Erik H; Hart, Margreet M; Loeff, Floris C.; Dijk, Lisanne; Derksen, Ninotska I. L.; Wieringa, Roeland; Leeuwen, W.A. van; Krieckaert, C.; Vries, Annick de; Nurmohamed, M.T.; Wolbink, Gertjan; Rispens, Theo

doi:10.55563/clinexprheumatol/nlr4r8

Cited by 14 publications

(11 citation statements)

References 25 publications

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“…There is evidence that ADAs were still detected at higher certolizumab concentrations of >10 mg/l. 59 The majority of patients with ADA had detectable titres from week 16 onwards, and 65% remained ADA positive after 1 year of follow up. 59 There are no studies in paediatric populations.…”

Section: Impact Of Immunogenicity On Clinical Efficacy and Toxicity P...mentioning

confidence: 86%

“…59 The majority of patients with ADA had detectable titres from week 16 onwards, and 65% remained ADA positive after 1 year of follow up. 59 There are no studies in paediatric populations.…”

Section: Impact Of Immunogenicity On Clinical Efficacy and Toxicity P...mentioning

confidence: 86%

“…37 Studies in both paediatric and adult populations did not report an association between ADAs and adverse effects to golimumab. 39,56,57 Similarly, multiple adult studies reported no association between the presence of ADAs against certolizumab and adverse effects; 42,43,59 in addition, RA patients who experienced adverse effects did not have ADAs. 42,43 Immunogenicity to anti-TNF-α biosimilars is similar to or lower than that of their originators Biosimilars are new biological products which are highly similar to their biological reference drug and have comparable clinical efficacy.…”

Section: Adas Against Infliximab and Adalimumab Have Been Associated ...mentioning

confidence: 99%

“…Studies in both paediatric and adult populations did not report an association between ADAs and adverse effects to golimumab. 39,56,57 Similarly, multiple adult studies reported no association between the presence of ADAs against certolizumab and adverse effects; 42,43,59 in addition, RA patients who experienced adverse effects did not have ADAs. 42,43…”

Section: Introductionmentioning

confidence: 98%

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Impact of immunogenicity on clinical efficacy and toxicity profile of biologic agents used for treatment of inflammatory arthritis in children compared to adults

Parikh

Ponnampalam

Seligmann

et al. 2021

Therapeutic Advances in Musculoskeletal

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The treatment of inflammatory arthritis has been revolutionised by the introduction of biologic treatments. Many biologic agents are currently licensed for use in both paediatric and adult patients with inflammatory arthritis and contribute to improved disease outcomes compared with the pre-biologic era. However, immunogenicity to biologic agents, characterised by an immune reaction leading to the production of anti-drug antibodies (ADAs), can negatively impact the therapeutic efficacy of biologic drugs and induce side effects to treatment. This review explores for the first time the impact of immunogenicity against all licensed biologic treatments currently used in inflammatory arthritis across age, and will examine any significant differences between ADA prevalence, titres and timing of development, as well as ADA impact on therapeutic drug levels, clinical efficacy and side effects between paediatric and adult patients. In addition, we will investigate factors associated with differences in immunogenicity across biologic agents used in inflammatory arthritis, and their potential therapeutic implications.

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Section: Impact Of Immunogenicity On Clinical Efficacy and Toxicity P...mentioning

confidence: 86%

Section: Impact Of Immunogenicity On Clinical Efficacy and Toxicity P...mentioning

confidence: 86%

Section: Adas Against Infliximab and Adalimumab Have Been Associated ...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

See 2 more Smart Citations

Impact of immunogenicity on clinical efficacy and toxicity profile of biologic agents used for treatment of inflammatory arthritis in children compared to adults

Parikh

Ponnampalam

Seligmann

et al. 2021

Therapeutic Advances in Musculoskeletal

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show abstract

“…Six etanercept‐treated patients who did not start etanercept treatment at Week 4 and five etanercept‐treated patients without samples available for TNF measurements were excluded. The fourth cohort consisted of 20 consecutive certolizumab‐treated RA patients (Berkhout, Vogelzang, et al, 2020). A loading dose of 400 mg of certolizumab was administered subcutaneously at Weeks 0, 2 and 4, followed by 200 mg once every 2 weeks.…”

Section: Methodsmentioning

confidence: 99%

Formation and clearance of TNF–TNF inhibitor complexes during TNF inhibitor treatment

Berkhout,

I'Ami,

Kruithof

et al. 2023

British J Pharmacology

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Background and purposeMillions of patients with inflammatory diseases are treated with TNF inhibitors (TNFi). Individual treatment response varies, in part related to variable drug clearance. The role of TNF‐TNFi complexes in clearance of the different TNFi is controversial. Moreover, mechanistic insight into the structural aspects and biological significance of TNF‐TNFi complexes is lacking. We hypothesized a role for Fc‐mediated clearance of TNF‐TNFi immune complexes. Therefore, we investigated circulating TNF‐TNFi complexes upon treatment with certolizumab – lacking Fc tails – in comparison to adalimumab, golimumab, infliximab and etanercept.Experimental ApproachDrug‐tolerant ELISAs were developed and used to quantify TNF during adalimumab (n=193), golimumab (n=26), etanercept (n=186), certolizumab (n=20) and infliximab (n=29) treatment in patients with inflammatory arthritis or ulcerative colitis for a maximum follow‐up of one year. Effect on in vitro TNF production and Fc‐mediated uptake of TNF‐TNFi complexes were investigated for all five TNFi.Key ResultsCirculating TNF concentrations were >20‐fold higher during certolizumab treatment compared to adalimumab, reaching up to 23.1 ng/mL. Internalization of TNF‐TNFi complexes by macrophages critically depended on Fc valency: efficient uptake for the full antibody TNFi (three Fc tails), but little or no uptake for etanercept and certolizumab (one and zero Fc tail, respectively). TNF production was not affected by TNFi. These findings also allowed estimation of total TNF load, which appears insufficient to significantly impact clearance rate of total TNFi.Conclusions and ImplicationsDifferences in TNFi structure profoundly impact the clearance of TNF, while it is unlikely that TNF itself significantly contributes to target‐mediated drug disposition of TNFi.

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Certolizumab-induced sarcoidosis in a patient with psoriatic arthritis – a case report and review of literature

Biernikowicz,

Pilch,

Wojturska

et al. 2024

Rheumatol Int

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Tumour necrosis factor-α (TNF- α) antagonists are considered a significant therapeutic option in the treatment of sarcoidosis. Nevertheless, their use can also paradoxically result in sarcoidosis-like reactions. Here, we present a case of a 56-year-old patient with psoriatic arthritis who after 3 months of certolizumab therapy developed pulmonary sarcoidosis. Therefore, certolizumab was discontinued and prednisone initiated. Subsequently, 4 months later a complete remission of interstitial lesions was observed. Due to insufficient control of psoriatic arthritis, upadacitinib and methotrexate were prescribed and despite initial improvement, a couple of months later a massive exacerbation of skin psoriasis occurred and the treatment was switched to secukinumab. As of today, no evidence of sarcoidosis recurrence has been noted. Drug-induced sarcoidosis-like reactions (DISR) appear to be less frequently associated with certolizumab rather than with other anti-TNF-α agents. However, specific mechanisms of this phenomenon remain unclear and require future investigation.

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The effect of certolizumab drug concentration and anti-drug antibodies on TNF neutralisation

Cited by 14 publications

References 25 publications

Impact of immunogenicity on clinical efficacy and toxicity profile of biologic agents used for treatment of inflammatory arthritis in children compared to adults

Impact of immunogenicity on clinical efficacy and toxicity profile of biologic agents used for treatment of inflammatory arthritis in children compared to adults

Formation and clearance of TNF–TNF inhibitor complexes during TNF inhibitor treatment

Certolizumab-induced sarcoidosis in a patient with psoriatic arthritis – a case report and review of literature

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