Dose–escalation of adalimumab, golimumab or ustekinumab in inflammatory bowel diseases: characterization and implications in real-life clinical practice

Ylisaukko-oja, Tero; Puttonen, Minna; Jokelainen, Jari; Koivusalo, Mirkka; Tamminen, Klaus; Torvinen, Saku; Voutilainen, Markku

doi:10.1080/00365521.2021.2014950

Cited by 6 publications

(8 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Among the 63 publications, 10‐72 58 were journal articles and 5 were international conference abstracts. Two conference abstracts 71,72 were replaced by subsequent published articles found in our search.…”

Section: Resultsmentioning

confidence: 99%

Meta‐analysis: Persistence of advanced therapies in the treatment of inflammatory bowel disease

Yiu,

Ko,

Pudipeddi

et al. 2024

Aliment Pharmacol Ther

View full text Add to dashboard Cite

SummaryBackgroundThe expanding options in advanced therapies for ulcerative colitis (UC) and Crohn's disease (CD) present challenges in treatment selection. Persistence analysis assesses drug durability in real‐world settings, acting as a surrogate marker for medication efficacy and tolerance. Unlike traditional comparative studies, persistence analysis provides insights extending beyond the initial year of treatment.AimTo provide real‐world evidence on treatment effectiveness, tolerability and preferences of physicians and patients regarding various advanced therapies for IBD.MethodsWe conducted a systematic review of observational studies up to March 2023 assessing advanced therapies' persistence in UC and CD. Advanced therapies under examination included infliximab, adalimumab, vedolizumab, ustekinumab, golimumab, certolizumab and tofacitinib. We pooled the persistence of each agent and conducted a meta‐analysis to compare the persistence of newer agents with traditional TNF inhibitors (TNFi)—specifically infliximab and adalimumab.ResultsAmong 63 observational studies, vedolizumab had the highest 1‐year persistence in UC (73.8%, 95% CI: 70.0%–77.6%) and ustekinumab in CD (77.5%, 95% CI: 72.9%–82.1%). Compared to TNFi, vedolizumab demonstrated increased persistence with a relative risk (RR) of 1.30 (95% CI: 1.19–1.41) for UC and 1.14 (95% CI: 1.09–1.20) for CD at 1 year, while ustekinumab demonstrated a RR of 1.15 (95% CI: 1.07–1.23) for CD at 1 year. Vedolizumab exhibited sustained increased persistence in UC over 2 years compared to TNFi (RR: 1.33, 95% CI 1.14–1.54).ConclusionThis meta‐analysis highlights the superior persistence of ustekinumab and vedolizumab over TNFi, and offers valuable insights for clinicians navigating the challenging landscape of UC and CD therapeutic choices.

show abstract

Section: Resultsmentioning

confidence: 99%

Meta‐analysis: Persistence of advanced therapies in the treatment of inflammatory bowel disease

Yiu,

Ko,

Pudipeddi

et al. 2024

Aliment Pharmacol Ther

View full text Add to dashboard Cite

show abstract

“…27 Our study found 1-year persistence rates of 86.5% for UST and 57.9% for VDZ treatment, which are higher than the rates found by Ylisaukko-Oja et al of 46.2%-37.1% for ADA and 47.1% for UST during 12 months of treatment in a real-life setting. 28 In this study, regression models were created to identify the significant predictors of achieving SFR at week 52. The regressions showed that baseline UST treatment and lower treatment line were significant predictors of outcomes, although the Nagelkerke R 2 of the models indicated only weak correlations.…”

Section: Discussionmentioning

confidence: 99%

“… 27 Our study found 1-year persistence rates of 86.5% for UST and 57.9% for VDZ treatment, which are higher than the rates found by Ylisaukko-Oja et al of 46.2%–37.1% for ADA and 47.1% for UST during 12 months of treatment in a real-life setting. 28 …”

Section: Discussionmentioning

confidence: 99%

Ustekinumab is associated with superior treatment persistence but not with higher remission rates versus vedolizumab in patients with refractory Crohn’s disease: results from a multicentre cohort study

Bacsúr

Matuz

Resál

et al. 2022

Therap Adv Gastroenterol

View full text Add to dashboard Cite

Background: Treatment with antitumor necrosis factor alpha (anti-TNF-α) is safe and effective as first-line therapy; however, its efficacy is limited due to primary nonresponse (PNR) and secondary loss of response (LOR), resulting in treatment discontinuation in approximately 40%–50% of cases. Vedolizumab (VDZ) and ustekinumab (UST) therapies could be good alternatives in patient with anti-TNF failure; however, no head-to-head randomized comparison of these drugs as second- or third-line treatments has been made. Objectives: This study aimed to assess the treatment persistence and comparative effectiveness of UST and VDZ in patients with refractory Crohn’s disease (CD). Design: In this nationwide retrospective study, patients with CD on UST or VDZ maintenance therapy were enrolled. Clinical data at baseline, after induction, and at week 52 were obtained. Methods: Clinical and biochemical activities as well as corticosteroid-free remission (SFR) rates were assessed, while concomitant medications, comorbidities, hospitalizations, and surgeries were recorded during the follow-up to detect any predictors. Results: A total of 161 UST- and 65 VDZ-treated patients completed the follow-up. No significant difference in clinical or biochemical remission rates was observed after induction between the two treatment groups; however, clinical remission rate at week 52 was higher in UST group. UST showed superior drug persistence than VDZ (86.5%, 57.9%, p < 0.0001). The drug type was predictive of clinical SFR at week 52 [ p = 0.011, odds ratio (OR) = 2.39 with UST]. Drug failure rates were higher for VDZ than those for UST (PNR rates: 21.54% and 4.97%, respectively, p < 0.001, OR = 8.267, p = 0.001). LOR and escalations were more common during UST treatment (61.5% versus 36.9%, p < 0.001; 64.2% versus 23.1%, p < 0.001). Hospital and surgical admission rates did not differ significantly. Only one adverse event occurred with VDZ at week 20, which led to drug cessation. Conclusions: VDZ and UST were safe and effective for treating patients with CD in whom anti-TNF therapy failed. UST showed superior drug persistence than VDZ, but dose escalation was more frequent. Biologicals used in lower treatment lines resulted in better drug persistence.

show abstract

“…Although these trials showed a greater efficacy of golimumab compared to placebo, up to 40% lost their response during maintenance therapy and the PURSUIT‐M study failed to define an optimisation strategy 2 . Few real‐life studies had reported effectiveness of dose intensification in UC patients with loss of response to golimumab and assessment of dose flexibility was limited to dose titration to higher doses with the same dosing interval, every 4 weeks 3–8 …”

Section: Introductionmentioning

confidence: 99%

“…2 Few real-life studies had reported effectiveness of dose intensification in UC patients with loss of response to golimumab and assessment of dose flexibility was limited to dose titration to higher doses with the same dosing interval, every 4 weeks. [3][4][5][6][7][8] Reactive therapeutic drug monitoring (TDM) is used in daily clinical practice in the event of loss of response to identify mechanism of drug failure. From an individual perspective, TDM guides clinician to choose the best therapeutic decision.…”

Section: Introductionmentioning

confidence: 99%

Effectiveness of golimumab intensification in ulcerative colitis: A multicentric prospective study

Fuméry

Nancey

Filippi³

et al. 2023

Aliment Pharmacol Ther

View full text Add to dashboard Cite

Summary Introduction Loss of response to golimumab occurs in nearly 40% of patients with ulcerative colitis (UC). Unlike others anti‐TNF, no study has reported a correlation between serum golimumab level and response to drug intensification. The objective of this study was to evaluate the effectiveness and safety of golimumab intensification and to identify the best threshold of serum golimumab before drug intensification predictive of response. Patients and Methods We included all consecutive patients with active UC with loss of response to golimumab in a prospective multicentric cohort study. Patients with loss of response at 50 mg q4 weeks (W) and 100 mg q4W underwent therapeutic intensification at 100 mg q4W and 100 mg q2W, respectively. Effectiveness and safety were assessed between Weeks 2 and 4 (visit 2) and between Weeks 4 and 8 (visit 3) after intensification. Serum level and anti‐golimumab antibodies were evaluated at each medical visit (Lisa Tracker, Theradiag France). Results A total of 47 UC patients (Female, 50%; median age, 39 years (IQR, 27–52)) treated with golimumab for a median of 20.4 weeks (IQR, 10.7–38.3) were included. The median partial Mayo score was 6 (IQR, 5–7), and the median endoscopic Mayo score was 3 (IQR, 2–3). The median golimumab serum level before intensification was 2.23 μg/mL (IQR, 1.02–3.96) and only one patient (2.1%) had anti‐drug antibodies. At Visit 2 (Week 2–4), 40% patients experienced clinical response, 10% clinical remission, 33% endoscopic response and 23% endoscopic remission. At Visit 3 (Week 4–8), 44% of patients had clinical response, 22% of patients had clinical remission, 45% of patients had endoscopic response, and 41% of patients had endoscopic remission. The median golimumab levels before intensification do not differ between responders and non‐responders (2.13 μg/ml (0.76–2.76) and 3.37 μg/ml (IQR, 1.08–4.67), respectively; p = 0.14) assessed at Visit 3. Golimumab intensification to 100 mg q4W (vs q2W) (OR 1.98, 95% CI [1.06–3.70]; p = 0.032) was significantly associated with clinical remission at Visit 3. Serum drug level at baseline or the presence of antidrug antibodies were not associated with clinical or endoscopic remission/response. Two serious adverse events (one infection and one UC flare) were reported during the 24‐week follow‐up. Conclusion In this prospective multicentric study, half of patients recaptured response following golimumab intensification in UC. Therapeutic drug monitoring did not predict response after optimisation of golimumab.

show abstract

Dose–escalation of adalimumab, golimumab or ustekinumab in inflammatory bowel diseases: characterization and implications in real-life clinical practice

Cited by 6 publications

References 31 publications

Meta‐analysis: Persistence of advanced therapies in the treatment of inflammatory bowel disease

Meta‐analysis: Persistence of advanced therapies in the treatment of inflammatory bowel disease

Ustekinumab is associated with superior treatment persistence but not with higher remission rates versus vedolizumab in patients with refractory Crohn’s disease: results from a multicentre cohort study

Effectiveness of golimumab intensification in ulcerative colitis: A multicentric prospective study

Contact Info

Product

Resources

About