Introduction
While the therapeutic armamentarium for Crohn’s disease (CD) is rapidly expanding, direct evidence on comparative efficacy of various treatments is lacking1. CT-P13 subcutaneous (SC) provides patients with a new opportunity for maintenance treatment of their disease2.
Aims & Methods
To place CT-P13 SC into the perspective of other therapies and to address knowledge gaps, a network meta-analysis (NMA) was conducted to evaluate comparative efficacy of licensed biologics using data from phase 3 randomised controlled trials (RCTs) in CD published to date. Studies were identified through literature searches that included publications up to 31 March 2023. Phase 3 RCTs evaluating biologics approved by the European Medicines Agency or United States Food and Drug Administration as of 31 March 2023 for maintenance treatment of adult patients with moderate-to-severe CD3,4 were included, i.e. infliximab (IFX) intravenous (IV) and SC, adalimumab (ADL) SC, vedolizumab (VDZ) IV and SC, ustekinumab (UST) SC, and risankizumab (RZB) SC. Eligible studies evaluated the efficacy of maintenance therapy with follow-up periods of 52–64 weeks in patients who responded to induction treatment. Each study was controlled with placebo (PBO) or an active comparator. Head-to-head studies directly comparing efficacy of licensed biologics in CD (including those with treat-through designs) were also considered for inclusion. Clinical remission rates achieved with standard doses of each biologic were synthesised and analysed in a Bayesian NMA fixed-effect model. Rank probabilities of each comparator arm were summarised with surface under the cumulative ranking curve (SUCRA) values.
Results
Overall, 8 RCTs were identified and included in the analysis (ACCENT I, LIBERTY-CD, CHARM, SEAVUE, GEMINI 2, VISIBLE 2, IM-UNITI, FORTIFY)5–12. Most studies enrolled both naïve and biologic- and/or Janus kinase inhibitor-exposed patients, apart from ACCENT-1 and SEAVUE which enrolled only anti-tumour necrosis factor- and biologic-naïve patients, respectively. The present NMA was conducted using data pooled from all patients. A network of evidence was constructed, enabling comparative analysis of relative effect size versus PBO. Among 8 comparator arms, IFX SC 120 mg every 2 weeks (Q2W) showed the highest odds ratio (95% confidence interval [CI]) vs. PBO for clinical remission during the maintenance phase (3.52 [2.18–5.65]), followed by ADL SC 40 mg Q2W (2.92 [1.90–4.47]), UST SC 90 mg every 8 weeks (Q8W) (2.79 [1.85–4.21]), IFX IV 5 mg/kg Q8W (2.55 [1.29–5.27]), VDZ IV 300 mg Q8W (2.33 [1.43–3.86]), RZB SC 180 mg Q8W (1.80 [1.15–2.84]), VDZ SC 108 mg Q2W (1.76 [1.14–2.70]), and RZB SC 360 mg Q8W (1.60 [1.00–2.52]). In addition, IFX SC 120 mg Q2W ranked highest for clinical remission in terms of SUCRA values (0.887), followed by ADL SC 40 mg Q2W (0.763), UST SC 90 mg Q8W (0.718), IFX IV 5 mg/kg Q8W (0.630), VDZ IV 300 mg Q8W (0.566), RZB SC 180 mg Q8W (0.353), VDZ SC 108 mg Q2W (0.327), RZB SC 360 mg Q8W (0.252), and PBO (0.005).
Conclusion
In this updated NMA on the comparative efficacy of licensed biologics for CD, IFX SC 120 mg Q2W ranked first for achieving clinical remission during maintenance treatment of 52–64 weeks’ duration in patients with moderate-to-severe CD.
References
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Disclosure
Stefan Schreiber has served as a consultant or advisory board member for AbbVie, Amgen, Arena, Bristol Myers Squibb, Biogen, Celltrion, Celgene, Falk, Ferring, Fresenius, Galapagos, Gilead, IMAB, Janssen, Lilly, MSD, Mylan, Pfizer, Protagonist, Provention Bio, Sandoz/Hexal, Takeda, Theravance, and UCB; and received lecture fees from HIKMA.
Silvio Danese reports consultancy fees from AbbVie, Alimentiv, Allergan, Amgen, Applied Molecular Transport, AstraZeneca, Athos Therapeutics, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Dr Falk Pharma, Eli Lilly, Enthera, Ferring Pharmaceuticals Inc., Gilead, Hospira, Inotrem, Janssen, Johnson & Johnson, Morphic, MSD, Mundipharma, Mylan, Pfizer, Roche, Sandoz, Sublimity Therapeutics, Takeda, Teladoc Health, TiGenix, UCB Inc., Vial, and Vifor; and lecture fees from AbbVie, Amgen, Ferring Pharmaceuticals Inc., Gilead, Janssen, Mylan, Pfizer, and Takeda.
Jean-Frederic Colombel reports receiving research grants from AbbVie, Bristol Myers Squibb, Janssen Pharmaceuticals, and Takeda; payment for lectures from AbbVie and Takeda; consulting fees from AbbVie, Allergan, Amgen, AnaptysBio, Arena Pharmaceuticals, Boehringer Ingelheim, Bristol Myers Squibb, Celgene Corporation, Celltrion, Eli Lilly, Ferring Pharmaceuticals, Galmed Research, Glaxo Smith Kline, Genentech (Roche), Immunic, Invea, Iterative Scopes, Janssen Pharmaceuticals, Kaleido Biosciences, Landos, Merck, Microba Life Science, Novartis, Otsuka Pharmaceutical, Pfizer, Prometheus, Protagonist Therapeutics, Sanofi, Seres, Takeda, Teva, TiGenix, and Vifor; and holds stock options in Intestinal Biotech Development.
Tadakazu Hisamatsu has received honoraria and had expenses paid to attend or give a presentation/advice at a meeting for AbbVie GK, EA Pharma Co. Ltd, Gilead Sciences, Janssen Pharmaceutical K.K., JIMRO Co., Ltd, KISSEI PHARMACEUTICAL CO., LTD, Kyorin Pharmaceutical Co., Ltd, Mitsubishi Tanabe Pharma Corporation, Mochida Pharmaceutical Co., Ltd, Nichi-Iko Pharmaceutical Co., Ltd, Pfizer Japan Inc., and Takeda Pharmaceutical Co., Ltd; research grants from Alfresa Pharma Corporation and EA Pharma Co., Ltd; and scholarship grants from AbbVie GK, Daiichi-Sankyo, EA Pharma Co., Ltd, JIMRO Co. Ltd, Kyorin Pharmaceutical Co., Ltd, Mitsubishi Tanabe Pharma Corporation, Mochida Pharmaceutical Co., Ltd, Nippon Kayaku Co., Ltd, Pfizer Japan Inc., Takeda Pharmaceutical Co., Ltd, and Zeria Pharmaceutical Co., Ltd.
Peter M. Irving reports lecture fees from AbbVie, BMS, Celgene, Celltrion, Falk Pharma, Ferring, Galapagos, Gilead, MSD, Janssen, Lilly, Pfizer, Takeda, Tillotts, Sapphire Medical, Sandoz, Shire, and Warner Chilcott; financial support for research from Celltrion, Galapagos, MSD, Pfizer, and Takeda; and advisory fees from AbbVie, Arena, Boehringer Ingelheim, BMS, Celgene, Celltrion, Genentech, Gilead, Hospira, Janssen, Lilly, MSD, Pfizer, Pharmacosmos, Prometheus, Roche, Sandoz, Samsung Bioepis, Takeda, Topivert, VH2, Vifor Pharma, and Warner Chilcott.
Hyunsoo Park is an employee of Celltrion Healthcare Co., Ltd.
Dong-Hyeon Kim is an employee of Celltrion Healthcare Co., Ltd.
Young Nam Lee is an employee of Celltrion Healthcare Co., Ltd.
Stephen B. Hanauer reports consultancy for AbbVie, Amgen, Boehringer Ingelheim, Celltrion, Fresenius Kabi, Janssen, Merck, and Samsung Bioepis; acting as a speaker for AbbVie and Janssen; and participating in Data and Safety Monitoring Boards for Boehringer Ingelheim.
Funding: This study was supported by Celltrion Healthcare Co., Ltd (Incheon, Republic of Korea). Editing support was provided by Beatrice Tyrrell, DPhil, CMPP (Aspire Scientific, Bollington, UK) and funded by Celltrion Healthcare Co., Ltd (Incheon, Republic of Korea).
