Randomised trial and open-label extension study of an anti-interleukin-6 antibody in Crohn’s disease (ANDANTE I and II)
Open accessAbstract
Objective: Neutralising pro-inflammatory interleukin-6 (IL-6) may effectively treat Crohn’s disease (CD). Effects of PF-04236921, an anti-IL-6 antibody, in adults with CD are reported. Design: Parallel-group, dose-ranging, double-blind trial with 4-week screening and 12-week treatment periods. After induction, patients entered 28-week follow-up or 48-week open-label extension (OLE) with 28-week follow-up. Adults with confirmed CD and inadequate response to anti-tumour necrosis factor (TNF) therapy were included. Induction study: 249 patients randomised 1:1:1:1 to placebo, PF-04236921 10, 50 or 200 mg by subcutaneous injection on days 1 and 28. OLE study: PF-04236921 50 mg every 8 weeks up to six doses followed by 28-week follow-up. Results: 247 patients were randomised and received treatment in the induction study. The 200 mg dose was discontinued due to safety findings in another study (NCT01405196) and was not included in the primary efficacy analysis. Crohn’s Disease Activity Index (CDAI)-70 response rates with PF-04236921 50 mg were significantly greater than placebo at weeks 8 (49.3% vs 30.6%, P<0.05) and 12 (47.4% vs 28.6%, P<0.05) and met the primary end point. Week 12 CDAI remission rates with PF-04236921 50 mg and placebo were 27.4% and 10.9%, respectively (16.5% difference; P<0.05). 191 subjects received treatment in the OLE. Common treatment-emergent and serious adverse events in both studies included worsening CD, abdominal pain and nasopharyngitis. Conclusions: PF-04236921 50 mg induced clinical response and remission in refractory patients with moderate-to-severe CD following failure of anti-TNF therapy. GI abscess and perforation were observed, a specific focus of attention during future clinical development. Trial registration number: NCT01287897 and NCT01345318.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Blocking IL-6 in IBD resulted in severe adverse effects, such as abdominal pain, rather than just ameliorating intestinal inflammation.
“Blocking IL-6 in IBD resulted in severe adverse effects, such as abdominal pain, rather than just ameliorating intestinal inflammation [110].”
From The double-edged effects of IL-6 in liver regeneration, aging, inflammation, and diseases (2024) · cites this paper as [110]
The Results (Safety outcomes; page unavailable) report abdominal pain as a common adverse event and serious events involving abscess or perforation in patients receiving the anti-IL-6 antibody. But the table does not identify abdominal pain specifically as severe, and the Discussion says it is difficult to distinguish the drug’s contribution to perforation or abscess from disease progression. The trial studied Crohn’s disease rather than IBD generally, and it also found a significant clinical response to treatment. (LLM, conf=0.88)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
No references could be resolved yet.
Research works printed but not linked: 14
- [1]Colombel JF, Sandborn WJ, Rutgeerts P, et al Adalimumab for maintenance of clinical response and remission in patients with Crohn’s disease: the CHARM trial. Gastroenterology 2007; 132: 52– 65. 10.1053/j.gastro.2006.11.041 17241859 · DOI
- [2]Hanauer SB, Feagan BG, Lichtenstein GR, et al Maintenance infliximab for Crohn’s disease: the ACCENT I randomised trial. Lancet 2002; 359: 1541– 9. 10.1016/S0140-6736(02)08512-4 12047962 · DOI
- [3]Sandborn WJ, Feagan BG, Stoinov S, et al Certolizumab pegol for the treatment of Crohn’s disease. N Engl J Med 2007; 357: 228– 38. 10.1056/NEJMoa067594 17634458 · DOI
- [4]Targan SR, Feagan BG, Fedorak RN, et al Natalizumab for the treatment of active Crohn’s disease: results of the ENCORE Trial. Gastroenterology 2007; 132: 1672– 83. 10.1053/j.gastro.2007.03.024 17484865 · DOI
- [5]Ding NS, Hart A, De Cruz P Systematic review: predicting and optimising response to anti-TNF therapy in Crohn’s disease - algorithm for practical management. Aliment Pharmacol Ther 2016; 43: 30– 51. 10.1111/apt.13445 26515897 · DOI
- [6]Allocca M, Jovani M, Fiorino G, et al Anti-IL-6 treatment for inflammatory bowel diseases: next cytokine, next target. Curr Drug Targets 2013; 14: 1508– 21. 10.2174/13894501113146660224 24102406 · DOI
- [7]Ito H, Takazoe M, Fukuda Y, et al A pilot randomized trial of a human anti-interleukin-6 receptor monoclonal antibody in active Crohn’s disease. Gastroenterology 2004; 126: 989– 96. 10.1053/j.gastro.2004.01.012 15057738 · DOI · Paper page
- [8]Fogel R, Sridharan S, Li C, et al AB0724 Safety, pharmacokinetics, and pharmacodynamics of a human anti-IL6 monoclonal antibody PF-04236921 in healthy subjects. Ann Rheum Dis 2013; 71 (Suppl.3): 680 10.1136/annrheumdis-2012-eular.724 · DOI
- [9]Wallace DJ, Strand V, Merrill JT, et al Efficacy and safety of an interleukin 6 monoclonal antibody for the treatment of systemic lupus erythematosus: a phase II dose-ranging randomised controlled trial. Ann Rheum Dis 2017; 76: 534– 42. 10.1136/annrheumdis-2016-209668 27672124 PMC5446001 · DOI
- [10]Curtis JR, Perez-Gutthann S, Suissa S, et al Tocilizumab in rheumatoid arthritis: a case study of safety evaluations of a large postmarketing data set from multiple data sources. Semin Arthritis Rheum 2015; 44: 381– 8. 10.1016/j.semarthrit.2014.07.006 25300699 · DOI
- [11]Gout T, Ostör AJ, Nisar MK Lower gastrointestinal perforation in rheumatoid arthritis patients treated with conventional DMARDs or tocilizumab: a systematic literature review. Clin Rheumatol 2011; 30: 1471– 4. 10.1007/s10067-011-1827-x 21833686 · DOI
- [12]Wilkins T, Jarvis K, Patel J Diagnosis and management of Crohn’s disease. Am Fam Physician 2011; 84: 1365– 75. 22230271
- [13]Sandborn WJ, Feagan BG, Rutgeerts P, et al Vedolizumab as induction and maintenance therapy for Crohn’s disease. N Engl J Med 2013; 369: 711– 21. 10.1056/NEJMoa1215739 23964933 · DOI
- [14]Feagan BG, Sandborn WJ, Gasink C, et al Ustekinumab as Induction and Maintenance Therapy for Crohn’s Disease. N Engl J Med 2016; 375: 1946– 60. 10.1056/NEJMoa1602773 27959607 · DOI
Cited by
Sorted by citations
Targeting IL-6 trans-signalling: past, present and future prospects
Rose-John, S., Jenkins, B. J., Garbers, C., Moll, J. M., & Scheller, J. (2023) · Nature Reviews Immunology · doi:10.1038/s41577-023-00856-y · Cited by 524 · see citing works
New insights into IL-6 family cytokines in metabolism, hepatology and gastroenterology
Giraldez, M. D., Carneros, D., Garbers, C., Rose-John, S., & Bustos, M. (2021) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-021-00473-x · Cited by 156 · see citing works
Immune-mediated inflammatory diseases: common and different pathogenic and clinical features
Monteleone, G., Moscardelli, A., Colella, A., Marafini, I., & Salvatori, S. (2023) · Autoimmunity Reviews · doi:10.1016/j.autrev.2023.103410 · Cited by 105 · see citing works
The double-edged effects of IL-6 in liver regeneration, aging, inflammation, and diseases
Wang, M.-J., Zhang, H.-L., Chen, F., Guo, X.-J., Liu, Q.-G., & Hou, J. (2024) · Experimental Hematology & Oncology · doi:10.1186/s40164-024-00527-1 · Cited by 84 · see citing works
“Blocking IL-6 in IBD resulted in severe adverse effects, such as abdominal pain, rather than just ameliorating intestinal inflammation [110].”
Background
- Authors
- Danese, S., Vermeire, S., Hellstern, P., Panaccione, R., Rogler, G., Fraser, G., Kohn, A., Desreumaux, P., Leong, R. W., Comer, G. M., Cataldi, F., Banerjee, A., Maguire, M. K., Li, C., Rath, N., Beebe, J., & Schreiber, S.
- Affiliations
- Humanitas University (IT)
- Universitair Ziekenhuis Leuven (BE)
- Nature Coast Clinical Research, Inverness, Florida, USA
- University of Calgary (CA)
- University of Zurich (CH)
- Tel Aviv University (IL)
- University of Crete (GR)
- Inserm (FR)
- Concord Hospital (US)
- Pfizer (United States) (US)
- Christian-Albrechts-Universität zu Kiel (DE)
- Corresponding author
- Danese, Silvio
- ORCID
- Venue
- Gut
- Publisher
- BMJ
- Published
- 2017-12-15
- Volume
- 68
- Issue
- 1
- Pages
- 40-48
- ISSN
- 0017-5749 (ISSN-L)
- 1468-3288
- PMC
- PMC6839832
- OpenAlex
- W2772378626
- Cited by
- 181
- References
- 0
- Citations by year
- 2026: 8 · 2025: 15 · 2024: 29 · 2023: 26 · 2022: 31 · 2021: 27 · 2020: 23 · 2019: 14 · 2018: 8
- FWCI
- 8.17
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- Gut (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- UNSWorks (University of New South Wales, Sydney, Australia) (submittedVersion, cc-by-nc-nd)
- Lirias (submittedVersion, cc-by-nc)
- Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Pfizer
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
- Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
- Health Sciences › Medicine › Ophthalmology › Ocular Diseases and Behçet’s Syndrome
- Keywords
- Crohn's disease, interleukin-6, anti-IL-6 antibody, refractory Crohn's disease, anti-TNF therapy failure, CDAI, remission, dose-ranging, open-label extension, adverse events, perforation, nasopharyngitis
- MeSH terms
- Adolescent, Adult, Aged, Crohn Disease, Double-Blind Method, Female, Humans, Male, Middle Aged, Severity of Illness Index, Treatment Outcome, Antibodies, Monoclonal, Humanized
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
