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Comparative Study
. 2024 Jun 3;18(6):790-800.
doi: 10.1093/ecco-jcc/jjad203.

Biologic Therapy for Inflammatory Bowel Disease: Real-World Comparative Effectiveness and Impact of Drug Sequencing in 13 222 Patients within the UK IBD BioResource

Christina Kapizioni  1   2 , Rofaida Desoki  1   3 , Danielle Lam  1   4 , Karthiha Balendran  1   5 , Eman Al-Sulais  1   6 , Sreedhar Subramanian  1 , Joanna E Rimmer  7 , Juan De La Revilla Negro  1 , Holly Pavey  8   9 , Laetitia Pele  10   11 , Johanne Brooks  12   13 , Gordon W Moran  14 , Peter M Irving  15   16 , Jimmy K Limdi  17   18 , Christopher A Lamb  19   20 ; UK IBD BioResource Investigators; Miles Parkes  1 , Tim Raine  1
Collaborators, Affiliations
Comparative Study

Biologic Therapy for Inflammatory Bowel Disease: Real-World Comparative Effectiveness and Impact of Drug Sequencing in 13 222 Patients within the UK IBD BioResource

Christina Kapizioni et al. J Crohns Colitis. .

Abstract

Background and aims: This study compares the effectiveness of different biologic therapies and sequences in patients with inflammatory bowel disease [IBD] using real-world data from a large cohort with long exposure.

Methods: Demographic, disease, treatment, and outcome data were retrieved for patients in the UK IBD BioResource. Effectiveness of treatment was based on persistence free of discontinuation or failure, analysed by Kaplan-Meier survival analysis with inverse probability of treatment weighting to adjust for differences between groups.

Results: In total, 13 222 evaluable patients received at least one biologic. In ulcerative colitis [UC] first-line vedolizumab [VDZ] demonstrated superior effectiveness over 5 years compared to anti-tumour necrosis factor [anti-TNF] agents [p = 0.006]. VDZ was superior to both infliximab [IFX] and adalimumab [ADA] after ADA and IFX failure respectively [p < 0.001 and p < 0.001]. Anti-TNF therapy showed similar effectiveness when used as first-line treatment, or after failure of VDZ. In Crohn's disease [CD] we found significant differences between first-line treatments over 10 years [p = 0.045], with superior effectiveness of IFX compared to ADA in perianal CD. Non-anti-TNF biologics were superior to a second anti-TNF after first-line anti-TNF failure in CD [p = 0.035]. Patients with UC or CD experiencing TNF failure due to delayed loss of response or intolerance had superior outcomes when switching to a non-anti-TNF biologic, rather than a second anti-TNF.

Conclusions: We provide real-world evidence to guide biologic selection and sequencing in a range of common scenarios. Our findings challenge current guidelines regarding drug selection after loss of response to first anti-TNF treatment.

Keywords: Crohn’s disease; biologic therapy; real-world effectiveness; sequencing; ulcerative colitis.

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Conflict of interest statement

GWM is a consultant with Alimentiv and has active research funding from AstraZeneca, Bristol Myers Squibb, Alimentiv, and Johnson & Johnson. GWM has active research collaborations with Motilent. CAL receives research support and/or has received fees for delivery of education from: Genentech, Janssen, Takeda, Abbvie, Dr Falk, AstraZeneca, Eli Lilly, Orion, Pfizer, Roche, Sanofi Aventis, Ferring, UCB, Nordic Pharma, and Biogen. JKL has received research support from Galapagos and Takeda and speaker and consultancy fees from Abbvie, Arena, Bristol Myers Squibb, Celltrion, Eli Lilly, Ferring, Galapagos, Janssen, MSD, Pfizer, and Takeda. MP receives research funding from Pfizer, Galapagos, and AstraZeneca. TR has received research/educational grants and/or speaker/consultation fees from Abbvie, Arena, Aslan, AstraZeneca, Boehringer-Ingelheim, BMS, Celgene, Eli Lilly, Ferring, Galapagos, Gilead, GSK, Heptares, LabGenius, Janssen, Mylan, MSD, Novartis, Pfizer, Roche, Sandoz, Takeda, UCB, and XAP therapeutics. PMI reports research grants from Celltrion, Pfizer, Takeda, and Galapagos; consulting fees from AbbVie, Arena, Boehringer-Ingelheim, BMS, Celltrion, Elasmogen, Gilead, Janssen, Lilly, Pfizer, Prometheus, and Sandoz; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AbbVie, BMS, Celgene, Celltrion, Falk Pharma, Galapagos, Gilead, Janssen, Lilly, Pfizer, Takeda, and Tillotts; and support for attending meetings and/or travel from Abbvie and Tillotts Pharma. SS has received speaker fees from Abbvie, Dr Falk pharmaceuticals, Takeda, Janssen, Celltrion,and Bristol-Myers Squibb, received educational grants from Abbvie, Takeda, and Janssen, and is an advisory board member for Abbvie, Dr Falk pharmaceuticals, Vifor pharmaceuticals, Janssen, Takeda, and Celltrion. SS is an associate editor for AP&T. RD received research support from Pfizer. CK, DL, EAS, KB, HP, LP, JR, JB, and JRN declare no conflict of interest.

Figures

Figure 1.
Figure 1.
Sequence and frequency of biologic selection for patients with Crohn’s disease [CD] and ulcerative colitis [UC] in the UK IBD BioResource. Sankey diagrams represent frequency of selection in different lines of therapy in patients with UC [A] and CD [B].
Figure 2.
Figure 2.
Effectiveness of first-line biologics in patients with ulcerative colitis [UC]. Kaplan–Meier plots depict survival free of treatment discontinuation or failure after inverse probability of treatment weighting adjustment for patients with UC treated for up to 5 years with different biologics as first-line therapy. Log-rank p-value as shown.
Figure 3.
Figure 3.
Effectiveness of first line biologics in patients with Crohn’s disease [CD]. Kaplan–Meier plots depict survival free of treatment discontinuation or failure after inverse probability of treatment weighting adjustment for patients with CD treated for up to 10 years with different biologics as first-line therapy. [A] All patients with CD receiving the indicated biologic therapy. [B] Subset of patients with CD and absence of perianal disease. [C] Subset of patients with CD and presence of perianal disease. Log-rank p values as shown.
Figure 4.
Figure 4.
Effectiveness of second-line biologics in patients with ulcerative colitis [UC] after failure of first-line anti-tumour necrosis factor. Kaplan–Meier plots depict survival free of treatment discontinuation or failure after inverse probability of treatment weighting adjustment for patients with UC treated for up to 3 years. [A] Patients treated with infliximab [red] or vedolizumab [blue] after failure of adalimumab [log-rank p < 0.001]. [B] Patients treated with adalimumab [red] or vedolizumab [blue] after failure of infliximab [log-rank p < 0.001].
Figure 5.
Figure 5.
Effectiveness of therapy in Crohn’s disease [CD] after failure of first-line anti-tumour necrosis factor [anti-TNF]. Kaplan–Meier plots depict survival free of treatment discontinuation or failure after inverse probability of treatment weighting adjustment for patients with CD treated for up to 3 years. [A–C] Use of a second anti-TNF [red] compared to a non-anti-TNF biologic [blue] as second-line therapy after failure of a first-line anti-TNF: [A] in all eligible patients with CD, [B] in patients who experienced primary non-response to first-line anti-TNF, and [C] in patients who experienced non-primary non-response to first-line anti-TNF. [D] Comparison of patients treated with vedlizumab [red] and ustekinumab [blue] as second- or third-line therapy after failure of prior anti-TNF therapy. Log-rank p values as shown.
Figure 6.
Figure 6.
Effectiveness of therapy in Crohn’s disease [CD] for individual biologics according to line of therapy. Kaplan–Meier plots depict survival free of treatment discontinuation or failure after inverse probability of treatment weighting adjustment for patients with CD treated for up to 3 years, according to whether the biologic was used prior to any other biologic [first line, red], after one previous biologic [second line, blue], after two other prior biologics [third line, green], or after three prior biologic therapies [fourth line, purple]. [A] Use of vedolizumab in different lines of therapy. [B] Use of ustekinumab in different lines of therapy. Log-rank p values as shown.
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