Effect of Therapeutic Drug Monitoring vs Standard Therapy During Maintenance Infliximab Therapy on Disease Control in Patients With Immune-Mediated Inflammatory Diseases

Syversen, Silje Watterdal; Jørgensen, Kristin Kaasen; Goll, Guro Løvik; Brun, Marthe Kirkesæther; Sandanger, Øystein; Bjørlykke, K. H.; Sexton, Joseph; Olsen, Inge Christoffer; Gehin, Johanna Elin; Warren, David J.; Klaasen, Rolf Anton; Noraberg, Geir; Bruun, Trude Jannecke; Dotterud, Christian Kvikne; Aga, Anna‐Birgitte; Haugen, Anne Julsrud; Njålla, Rune Johan; Zettel, Camilla; Ystrøm, Carl Magnus; Bragnes, Yngvill Hovde; Skorpe, Svanaug; Thune, Turid; Seeberg, Kathrine Aglen; Michelsen, Brigitte; Blomgren, Ingrid Marianne; Strand, Eldri Kveine; Mielnik, Paweł; Torp, Roald; Mørk, Cato; Kvien, Tore K; Jahnsen, Jørgen; Bolstad, Nils; Haavardsholm, Espen A.

doi:10.1001/jama.2021.21316

Cited by 79 publications

(59 citation statements)

References 48 publications

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“…There is currently insufficient evidence for the routine use of proactive TDM, in part because published cost-effectiveness analyses do not incorporate the current landscape of biopharmaceutical costs and usage. The NOR-DRUM trials were the first RCTs to assess the effectiveness of proactive TDM, as compared with standard therapy, across patients with immune-mediated inflammatory diseases, including RA, SpA and PsA 156 157. However, because of our inclusion date of 1 July 2020, we only included the abstract of NORDRUM A in our SLR124; meanwhile, full papers of both NOR-DRUM A and B have been published.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic drug monitoring of biopharmaceuticals in inflammatory rheumatic and musculoskeletal disease: a systematic literature review informing EULAR points to consider

et al. 2022

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The objectives of this review were to collect and summarise evidence on therapeutic drug monitoring (TDM) of biopharmaceuticals in inflammatory rheumatic and musculoskeletal diseases and to inform the EULAR Task Force for the formulation of evidence-based points to consider. A systematic literature review (SLR) was performed, covering technical aspects and (clinical) utility of TDM, to answer 13 research questions. MEDLINE, Embase and Cochrane were searched until July 2020. American College of Rheumatology and EULAR abstracts were also considered for inclusion. Data were extracted in evidence tables and risk of bias assessment was performed. For the search on technical aspects, 678 records were identified, of which 22 papers were selected. For the clinical utility search, 3846 records were identified, of which 108 papers were included. Patient-related factors associated with biopharmaceutical blood concentrations included body weight, methotrexate comedication and disease activity. The identification of a target range was hampered by study variability, mainly disease activity measures and study type. Evidence was inconsistent for multiple clinical situations in which TDM is currently applied. However, for some particular scenarios, including prediction of future treatment response, non-response to treatment, tapering and hypersensitivity reactions, robust evidence was found. There is currently no evidence for routine use of proactive TDM, in part because published cost-effectiveness analyses do not incorporate the current landscape of biopharmaceutical costs and usage. This SLR yields evidence in favour of TDM of biopharmaceuticals in some clinical scenarios, but evidence is insufficient to support implementation of routine use of TDM.

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Section: Discussionmentioning

confidence: 99%

Therapeutic drug monitoring of biopharmaceuticals in inflammatory rheumatic and musculoskeletal disease: a systematic literature review informing EULAR points to consider

et al. 2022

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“…No significant clinical benefits were shown for proactive TDM during infliximab induction therapy in patients with immune‐mediated inflammatory diseases (i.e., NOR‐DRUM A 22 ). During infliximab maintenance therapy, the clinical benefit of proactive TDM could also not be addressed in patients with IBD (i.e., TAXIT 23 and TAILORIX 24 ), yet it was addressed in a mixed population of patients with immune‐mediated inflammatory diseases (i.e., NOR‐DRUM B 25 ). Recently, the PRECISION 21 trial using a single‐model approach implemented in a Bayesian dashboard for infliximab dosing showed significant clinical benefit over label dosing during maintenance therapy.…”

Section: Discussionmentioning

confidence: 99%

Multi‐model averaging improves the performance of model‐guided infliximab dosing in patients with inflammatory bowel diseases

Kantasiripitak

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et al. 2022

CPT Pharmacom & Syst Pharma

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Infliximab dosage de-escalation without prior knowledge of drug concentrations may put patients at risk for underexposure and trigger the loss of response. A single-model approach for model-informed precision dosing during infliximab maintenance therapy has proven its clinical benefit in patients with inflammatory bowel diseases. We evaluated the predictive performances of two multimodel approaches, a model selection algorithm and a model averaging algorithm, using 18 published population pharmacokinetic models of infliximab for guiding dosage de-escalation. Data of 54 patients with Crohn's disease and ulcerative colitis who underwent infliximab dosage de-escalation after an earlier escalation were used. A priori prediction (based solely on covariate data) and maximum a posteriori prediction (based on covariate data and trough concentrations) were compared using accuracy and precision metrics and the classification accuracy at the trough concentration target of 5.0 mg/L. A priori prediction was inaccurate and imprecise, with the lowest classification accuracies irrespective of the approach (median 59%, interquartile range 59%-63%). Using the maximum a posteriori prediction, the model averaging algorithm had systematically better predictive performance than the model selection algorithm or the single-model approach with any model, regardless of the number of concentration data. Only a single trough concentration (preferably at the point of care) sufficed for accurate and precise prediction. Predictive performance of both single-and multi-model approaches was robust to the lack of covariate data. Model averaging using four models demonstrated similar predictive performance with a five-fold shorter computation time. This model averaging algorithm was implemented in the TDMx software tool to guide infliximab dosage de-escalation in the forthcoming prospective MODIFI study (NCT04982172).

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“…Recently, the NORwegian DRUg Monitoring study was published [ 124 ] to assess the efficacy of TDM in patients on infliximab treatment regarding the achievement of remission, as well as to maintain immune-mediated inflammatory disease control. Additionally, among patients with immune-mediated inflammatory diseases undergoing maintenance therapy with infliximab, proactive TDM was more effective than treatment without TDM in sustaining disease control without disease worsening [ 125 ]. For adalimumab, Menting et al [ 113 ] defined a window based on C trough from 3.51 to 7.00 μg/mL corresponding to the optimal clinical response.…”

Section: Therapeutic Drug Monitoring Of Monoclonal Antibodies In Psor...mentioning

confidence: 99%

Impact of Pharmacokinetic and Pharmacodynamic Properties of Monoclonal Antibodies in the Management of Psoriasis

et al. 2022

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The treatment of psoriasis has been revolutionized by the emergence of biological therapies. Monoclonal antibodies (mAb) generally have complex pharmacokinetic (PK) properties with nonlinear distribution and elimination. In recent years, several population pharmacokinetic/pharmacodynamic (PK/PD) models capable of describing different types of mAb have been published. This study aims to summarize the findings of a literature search about population PK/PD modeling and therapeutic drug monitoring (TDM) of mAb in psoriasis. A total of 22 articles corresponding to population PK/PD models of tumor necrosis factor (TNF)-α inhibitors (adalimumab and golimumab), interleukin (IL)-23 inhibitors (guselkumab, tildrakizumab, and risankizumab), IL-23/IL-12 inhibitor (ustekinumab), and IL-17 inhibitors (secukinumab, ixekizumab, and brodalumab) were collected. A summary of the clinical trials conducted so far in psoriasis was included, together with the current structural population PK and PD models. The most significant and clinical covariates were body weight (BW) and the presence of immunogenicity on clearance (CL). The lack of consensus on PK/PD relationships has prevented establishing an adequate dosage and, therefore, accentuates the need for TDM in psoriasis.

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Effect of Therapeutic Drug Monitoring vs Standard Therapy During Maintenance Infliximab Therapy on Disease Control in Patients With Immune-Mediated Inflammatory Diseases

Cited by 79 publications

References 48 publications

Therapeutic drug monitoring of biopharmaceuticals in inflammatory rheumatic and musculoskeletal disease: a systematic literature review informing EULAR points to consider

Therapeutic drug monitoring of biopharmaceuticals in inflammatory rheumatic and musculoskeletal disease: a systematic literature review informing EULAR points to consider

Multi‐model averaging improves the performance of model‐guided infliximab dosing in patients with inflammatory bowel diseases

Impact of Pharmacokinetic and Pharmacodynamic Properties of Monoclonal Antibodies in the Management of Psoriasis

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