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Predictors of drug survival: A cohort study comparing anti-tumour necrosis factor agents using the Swedish inflammatory bowel disease quality register
Örebro University, School of Medical Sciences. Department of Gastroenterology.ORCID iD: 0000-0002-6316-5027
Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Gastroenterology.ORCID iD: 0000-0002-1046-383x
Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
Örebro University, School of Medical Sciences. Örebro University Hospital. Clinical Epidemiology and Biostatistics.ORCID iD: 0000-0002-3552-9153
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2021 (English)In: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 54, no 7, p. 931-943Article in journal (Refereed) Published
Abstract [en]

Background: Whether long-term effectiveness differs between anti-tumour necrosis factor (anti-TNF) agents is unknown.

Aims: To examine drug survival of first-line anti-TNF agents and identify predictors of discontinuation. To reduce channelling bias, we also compared drug survival of the second anti-TNF.

Methods: Biologic-naive patients (N = 955) recorded in the Swedish IBD Quality Register (SWIBREG) were examined. We used propensity score matching, comparing drug survival over up to three years of follow-up. Cox regression estimated adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs).

Results: In Crohn's disease, discontinuation because of lack/loss of response was 32% [95%CI = 26%-38%] for infliximab versus 16% [95%CI = 11%-21%] for adalimumab. Infliximab [vs adalimumab; aHR = 1.96; 95%CI = 1.20-3.21] and colonic disease (L2) [vs no L2; aHR = 2.17; 95% CI = 1.26-3.75] were associated with higher discontinuation rates, whereas normalised CRP at three months [aHR = 0.40; 95% CI = 0.19-0.81] with a lower rate. Consistently, patients who switched from adalimumab to infliximab (vs infliximab to adalimumab) had earlier discontinuation (P = 0.04). Concomitant use of immunomodulators was associated with a lower adverse drug reaction-mediated discontinuation rate [aHR = 0.46; 95% CI = 0.28-0.77], in part explained by fewer infusion reactions [aHR = 0.27; 95% CI = 0.08-0.89]. In ulcerative colitis, the probability of discontinuation because of lack/loss of response was 40% [95% CI = 33%-47%] for infliximab versus 37% [95% CI = 21%-53%] for adalimumab. Disease duration >= 10 years [aHR = 0.25; 95% CI = 0.10-0.58] and normalised CRP after three months [aHR = 0.39; 95% CI = 0.18-0.84] were associated with lower discontinuation rates.

Conclusions: Clinical characterisation of patients may aid decision-making on anti-TNF treatment. The consistently shorter drug survival for infliximab (vs adalimumab) in Crohn's disease, suggests a potential difference between the two drugs.

Place, publisher, year, edition, pages
Blackwell Science Ltd. , 2021. Vol. 54, no 7, p. 931-943
National Category
Gastroenterology and Hepatology
Identifiers
URN: urn:nbn:se:oru:diva-93380DOI: 10.1111/apt.16525ISI: 000674338700001PubMedID: 34286871Scopus ID: 2-s2.0-85111428696OAI: oai:DiVA.org:oru-93380DiVA, id: diva2:1583400
Note

Funding agencies:

Research committee in Region Örebro County OLL-685891

Swedish government's agreement on medical training and research (ALF) OLL-929900 OLL-549221

Available from: 2021-08-06 Created: 2021-08-06 Last updated: 2025-02-11Bibliographically approved
In thesis
1. Biological treatment in inflammatory bowel disease: clinical and therapeutic aspects
Open this publication in new window or tab >>Biological treatment in inflammatory bowel disease: clinical and therapeutic aspects
2024 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Biological therapy has emerged as an important treatment modality for inflammatory bowel disease (IBD). Despite the prevailing trend, there contin­ues to be a lack of guidelines for selecting a suitable biological drug for a specific patient group. Register data are valuable sources for real-world studies of treatment outcomes across diverse patient groups. This thesis in­cludes four observational cohort studies assessing clinical and therapeutic aspects of biological treatment in patients with IBD, covering the main sub­types Crohn's disease and ulcerative colitis. The overarching aim is to ad­vance understanding of the effectiveness and safety of biological treatment in patients diagnosed with IBD.

Study I examined anti-tumour necrosis factor (anti-TNF) drug continuation rates in 955 patients with IBD that were recorded in the Swedish IBD regis­ter (SWIBREG). Infliximab (vs adalimumab) discontinuation was higher when used as first- and second-line treatment in patients with Crohn's dis­ease. Study II examined the use of golimumab in ulcerative colitis. Most (70%) of the 50 study patients were previously exposed to anti-TNF. After 1 year, 23 (46%) patients were still on golimumab treatment and improve­ments in clinical and biochemical markers were seen. Study III investigated long-term outcomes of vedolizumab treatment in patients participating in the extension of the Swedish observational study on vedolizumab, focusing on its effectiveness and use of healthcare resources in patients with IBD (SVEAH). Patients who initially responded to vedolizumab treatment and continued it beyond 1 year experienced high rates of clinical remission and improved quality of life measures after 3 years. Few serious adverse events were reported. Study IV examined correlations between baseline clinical characteristics, serum proteins, and drug levels post-induction. Four pro­teins of interest correlated with s-adalimumab levels.

This thesis proposes that the clinical and biochemical characterisation of patients with IBD can contribute to informed decision-making in biological treatment.

Place, publisher, year, edition, pages
Örebro: Örebro University, 2024. p. 132
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 308
Keywords
inflammatory bowel disease, Crohn's disease, ulcerative colitis, real-world data, SWIBREG, register-based studies, biological treatment, anti-TNF, integrin inhibitor, clinical effectiveness, biochemical data
National Category
General Practice
Identifiers
urn:nbn:se:oru:diva-116240 (URN)9789175296104 (ISBN)9789175296111 (ISBN)
Public defence
2024-12-12, Örebro universitet, Campus USÖ, Tidefeltsalen, Södra Grev Rosengatan 32, Örebro, 09:15 (English)
Opponent
Supervisors
Available from: 2024-09-24 Created: 2024-09-24 Last updated: 2024-12-16Bibliographically approved

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Visuri, IsabellaEriksson, CarlCao, YangMontgomery, ScottLudvigsson, Jonas F.Halfvarson, Jonas

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