How, When, and for Whom Should We Perform Therapeutic Drug Monitoring?

Vermeire, Séverine; Dreesen, Erwin; Papamichael, Konstantinos; Dubinsky, Marla

doi:10.1016/j.cgh.2019.09.041

Cited by 67 publications

(59 citation statements)

References 80 publications

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“…Currently, no data exists to identify which patients are more likely to benefit from dose escalation, and management of attenuated response is based on clinical judgment. As for anti-TNF therapy, therapeutic drug monitoring with incorporation of pharmacokinetic data in developing a management algorithm for primary and secondary failure will likely become a A c c e p t e d M a n u s c r i p t mainstay of therapy, identifying appropriate patients needing a rescue dose (11)(12)(13). In the UNITI program, serum concentrations of ustekinumab were proportional to dose, and associated with clinical efficacy (1,14).…”

Section: Discussionmentioning

confidence: 99%

Effectiveness and Safety of Ustekinumab Intensification at 90 mg Every 4 Weeks in Crohn’s Disease: A Multicentre Study

Fuméry

Peyrin–Biroulet

Nancey

et al. 2020

Journal of Crohn's and Colitis

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Introduction The approved maintenance regimens for ustekinumab in Crohn’s disease (CD) are 90 mg every 8 or 12 weeks. Some patients will partially respond to ustekinumab or will experience a secondary loss of response. It remains poorly known if these patients may benefit from shortening the interval between injections Methods All patients with active CD, as defined by Harvey-Bradshaw score ≥ 4 and one objective sign of inflammation (CRP > 5 mg/L and/or fecal calprotectin > 250 µg/g and/or radiologic and/or endoscopic evidence of disease activity) who required ustekinumab dose escalation to 90mg every 4 weeks for loss of response or incomplete response to ustekinumab 90mg every 8 weeks were included in this retrospective multicenter cohort study. Results One hundred patients, with a median age of 35 years (Interquartile Range (IQR), 28 – 49) and median disease duration of 12 (7 – 20) years were included. Dose intensification was performed after a median of 5.0 (2.8 - 9.0) months of ustekinumab treatment and was associated with corticosteroids and immunosuppressants in respectively 29% and 27% of cases. Short-term clinical response and clinical remission were observed in respectively 61% and 31% after a median of 2.4 (1.3 - 3.0) months. After a median follow-up of 8.2 (5.6-12.4) months, 61% of patients were still treated with ustekinumab, and 26% in steroid-free clinical remission. Among the 39 patients with colonoscopy during follow-up, 14 achieved endoscopic remission (no ulcers). At the end of follow-up, 27% of patients were hospitalized, and 19% underwent intestinal resection surgery. Adverse events were reported in 12% of patients, including five serious adverse events. Conclusion In this multicenter study, two-thirds of patients recaptured response following treatment intensification with ustekinumab 90 mg every 4 weeks.

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Section: Discussionmentioning

confidence: 99%

Effectiveness and Safety of Ustekinumab Intensification at 90 mg Every 4 Weeks in Crohn’s Disease: A Multicentre Study

Fuméry

Peyrin–Biroulet

Nancey

et al. 2020

Journal of Crohn's and Colitis

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“…The second is entitled "proactive" TDM, in which the quantification drug levels and/or antibodies is performed before failure, in all patients, allowing therapeutic adjustments to prevent both primary and secondary nonresponses. 32 Currently, the use of reactive TDM may be of benefit as www.irjournal.org compared to empirical change of therapy, owing to a reduction in the duration of an ineffective therapy, lower overall costs and to an increase in quality of life after therapeutic adjustment, drug levels and endoscopic remission. 33,34 There is still some uncertainty about the proper use of proactive TDM, once prospective trials comparing empirical or reactive changes in therapy demonstrated conflicting results.…”

Section: Tdm In Ibd: Concepts and Applicationsmentioning

confidence: 99%

Correlation of serum levels of anti-tumor necrosis factor agents with perianal fistula healing in Crohn’s disease: a narrative review

2021

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overall CD patients 3 and more than 90% of patients with rectal involvement. 4 The management of PFCD is multidisciplinary, with intensive medical therapy associated to multiple surgical procedures. This usually results in significant physical and psychological impact in patients' lives. There are significant limitations of conventional medical treatment in PFCD (corticosteroids, immunosuppressants, and antibiotics). Fistula healing rates are low with this strategy and recurrence is frequent. 5 Some prospective studies have demonstrated the efficacy of biologics in controlling perianal fistulas in CD. Present et al., 6 in the first randomized controlled study with biologics for the treatment of fistulizing CD, demonstrated the effectiveness of infliximab (IFX) in closing abdominal and perianal fistulas. Sands et al., 7 in the ACCENT 2 study, demonstrated the better efficacy of IFX as compared to

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“…The seminal extension study (IM-UNITI) ( 48 ) suggested 12-weekly maintenance dosing in biologic naive patients and 8-weekly dosing in anti-TNF therapy-experienced patients. Other ongoing trials include STARDUST (treat-to-target vs. routine case management in CD patients on UST), POWER (efficacy and safety of UST reinduction therapy in patients with moderate and severe CD), and RESCUE (loss of response to UST treated with dose escalation), which might help in guiding formulation of desired TLs for different therapeutic endpoints ( 49 ).…”

Section: Methodsmentioning

confidence: 99%

Advances in Therapeutic Drug Monitoring in Biologic Therapies for Pediatric Inflammatory Bowel Disease

Kapoor

Crowley

2021

Front. Pediatr.

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In the current era of treat-to-target strategies, therapeutic drug monitoring (TDM) has emerged as a potential tool in optimizing the efficacy of biologics for children diagnosed with inflammatory bowel disease (IBD). The incorporation of TDM into treatment algorithms, however, has proven to be complex. “Proactive” TDM is emerging as a therapeutic strategy due to a recently published pediatric RCT showing a clear benefit of “proactive” TDM in anti-TNF therapy. However, target therapeutic values for different biologics for different disease states [ulcerative colitis (UC) vs. Crohn's disease (CD)] and different periods of disease activity (induction vs. remission) require further definition. This is especially true in pediatrics where the therapeutic armamentarium is limited, and fixed weight-based dosing may predispose to increased clearance leading to decreased drug exposure and subsequent loss of response (pharmacokinetic and/or immunogenic). Model-based dosing for biologics offers an exciting insight into dose individualization thereby minimizing the chances of losing response. Similarly, point-of-care testing promises real-time assessment of drug levels and individualized decision-making. In the current clinical realm, TDM is being used to prolong drug durability and efficacy and prevent loss of response. Ongoing innovations may transform it into a personalized tool to achieve optimal therapeutic endpoints.

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How, When, and for Whom Should We Perform Therapeutic Drug Monitoring?

Cited by 67 publications

References 80 publications

Effectiveness and Safety of Ustekinumab Intensification at 90 mg Every 4 Weeks in Crohn’s Disease: A Multicentre Study

Effectiveness and Safety of Ustekinumab Intensification at 90 mg Every 4 Weeks in Crohn’s Disease: A Multicentre Study

Correlation of serum levels of anti-tumor necrosis factor agents with perianal fistula healing in Crohn’s disease: a narrative review

Advances in Therapeutic Drug Monitoring in Biologic Therapies for Pediatric Inflammatory Bowel Disease

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