Incidence rates of inflammatory bowel disease in patients with psoriasis, psoriatic arthritis and ankylosing spondylitis treated with secukinumab: a retrospective analysis of pooled data from 21 clinical trials

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Abstract

Objectives

Here, we present the reported incidence rates of inflammatory bowel disease (IBD) in patients receiving treatment with secukinumab for psoriasis (PsO), psoriatic arthritis (PsA) or ankylosing spondylitis (AS), in a pooled analysis of 21 clinical trials.

Methods

Data from all patients who had received at least one dose of secukinumab were included. Safety analyses were conducted to evaluate cumulative IBD rates as well as per-year rates, by indication. Crohn’s disease (CD), ulcerative colitis (UC) and IBD unclassified (IBDU) events were analysed using exposure-adjusted incidence rates (patient incidence rates per 100 patient-years (PY)).

Results

A total of 7355 patients with a cumulative exposure of 16 226.9 PY were included in the pooled analysis. Among 5181 patients with PsO, there were 14 cases of UC, 5 cases of CD and 1 case of IBDU, with exposure adjusted incidence rates (EAIRs) of 0.13, 0.05 and 0.01, respectively. Of these 20 cases, 14 were new-onset. In 1380 patients with PsA, there were 3 cases of UC, 3 cases of CD and 2 cases of IBDU (EAIRs 0.08, 0.08 and 0.05); 7 of these represented new-onset cases. Among 794 patients with AS, there were 4 cases of UC, 8 cases of CD and 1 case of IBDU (EAIRs 0.2, 0.4 and 0.1); 9 were new-onset cases. In the per year analysis, the EAIRs for each indication did not increase over time with secukinumab treatment.

Conclusions

In this pooled secukinumab safety analysis of 7355 patients across 21 clinical trials, cases of IBD events (including CD, UC and IBDU) were uncommon.

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Most cited references 40

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Analysis of five chronic inflammatory diseases identifies 27 new associations and highlights disease-specific patterns at shared loci

David Ellinghaus, Luke Jostins, Sarah L Spain … (2016)

We simultaneously investigated the genetic landscape of ankylosing spondylitis, Crohn's disease, psoriasis, primary sclerosing cholangitis and ulcerative colitis to investigate pleiotropy and the relationship between these clinically related diseases. Using high-density genotype data from more than 86,000 individuals of European-ancestry we identified 244 independent multi-disease signals including 27 novel genome-wide significant susceptibility loci and 3 unreported shared risk loci. Complex pleiotropy was supported when contrasting multi-disease signals with expression data sets from human, rat and mouse, and epigenetic and expressed enhancer profiles. The comorbidities among the five immune diseases were best explained by biological pleiotropy rather than heterogeneity (a subgroup of cases that is genetically identical to another disease, possibly due to diagnostic misclassification, molecular subtypes, or excessive comorbidity). In particular, the strong comorbidity between primary sclerosing cholangitis and inflammatory bowel disease is likely the result of a unique disease, which is genetically distinct from classical inflammatory bowel disease phenotypes.

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Inherited determinants of Crohn's disease and ulcerative colitis phenotypes: a genetic association study

Isabelle Cleynen, Gabrielle Boucher, Luke Jostins … (2016)

Summary Background Crohn's disease and ulcerative colitis are the two major forms of inflammatory bowel disease; treatment strategies have historically been determined by this binary categorisation. Genetic studies have identified 163 susceptibility loci for inflammatory bowel disease, mostly shared between Crohn's disease and ulcerative colitis. We undertook the largest genotype association study, to date, in widely used clinical subphenotypes of inflammatory bowel disease with the goal of further understanding the biological relations between diseases. Methods This study included patients from 49 centres in 16 countries in Europe, North America, and Australasia. We applied the Montreal classification system of inflammatory bowel disease subphenotypes to 34 819 patients (19 713 with Crohn's disease, 14 683 with ulcerative colitis) genotyped on the Immunochip array. We tested for genotype–phenotype associations across 156 154 genetic variants. We generated genetic risk scores by combining information from all known inflammatory bowel disease associations to summarise the total load of genetic risk for a particular phenotype. We used these risk scores to test the hypothesis that colonic Crohn's disease, ileal Crohn's disease, and ulcerative colitis are all genetically distinct from each other, and to attempt to identify patients with a mismatch between clinical diagnosis and genetic risk profile. Findings After quality control, the primary analysis included 29 838 patients (16 902 with Crohn's disease, 12 597 with ulcerative colitis). Three loci (NOD2, MHC, and MST1 3p21) were associated with subphenotypes of inflammatory bowel disease, mainly disease location (essentially fixed over time; median follow-up of 10·5 years). Little or no genetic association with disease behaviour (which changed dramatically over time) remained after conditioning on disease location and age at onset. The genetic risk score representing all known risk alleles for inflammatory bowel disease showed strong association with disease subphenotype (p=1·65 × 10−78), even after exclusion of NOD2, MHC, and 3p21 (p=9·23 × 10−18). Predictive models based on the genetic risk score strongly distinguished colonic from ileal Crohn's disease. Our genetic risk score could also identify a small number of patients with discrepant genetic risk profiles who were significantly more likely to have a revised diagnosis after follow-up (p=6·8 × 10−4). Interpretation Our data support a continuum of disorders within inflammatory bowel disease, much better explained by three groups (ileal Crohn's disease, colonic Crohn's disease, and ulcerative colitis) than by Crohn's disease and ulcerative colitis as currently defined. Disease location is an intrinsic aspect of a patient's disease, in part genetically determined, and the major driver to changes in disease behaviour over time. Funding International Inflammatory Bowel Disease Genetics Consortium members funding sources (see Acknowledgments for full list).

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Secukinumab is superior to ustekinumab in clearing skin of subjects with moderate to severe plaque psoriasis: CLEAR, a randomized controlled trial.

Diamant Thaçi, Andrew Blauvelt, Kristian Reich … (2015)

Secukinumab, a fully human anti-interleukin-17A monoclonal antibody, has shown superior efficacy to etanercept with similar safety in moderate to severe plaque psoriasis (FIXTURE study).

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Author and article information

Journal

Journal ID (nlm-ta): Ann Rheum Dis

Journal ID (iso-abbrev): Ann. Rheum. Dis

Journal ID (hwp): annrheumdis

Journal ID (publisher-id): ard

Title: Annals of the Rheumatic Diseases

Publisher: BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )

ISSN (Print): 0003-4967

ISSN (Electronic): 1468-2060

Publication date (Print): April 2019

Publication date (Electronic): 23 January 2019

Volume: 78

Issue: 4

Pages: 473-479

Affiliations

[1 ] departmentUniversity Hospital Schleswig Holstein , Christian-Alrechts-University , Kiel, Germany

[2 ] Icahn School of Medicine at Mount Sinai , New York City, New York, USA

[3 ] departmentRobarts Clinical Trials , Western University , London, Ontario, Canada

[4 ] Dermatologikum Berlin and SCIderm Research Institute , Hamburg, Germany

[5 ] Oregon Health & Science University , Portland, Oregon, USA

[6 ] University of Glasgow , Glasgow, UK

[7 ] Novartis Pharma AG , Basel, Switzerland

[8 ] Novartis Healthcare Pvt. Ltd , Hyderabad, Telangana, India

[9 ] Novartis Pharmaceuticals Corporation , East Hanover, New Jersey, USA

Author notes

[Correspondence to ] Professor Stefan Schreiber, University Hospital Schleswig Holstein, Christian-Alrechts-University, Kiel 24105, Germany; s.schreiber@ 123456mucosa.de

Author information

Atul A Deodhar http://orcid.org/0000-0002-2130-1246

Article

Publisher ID: annrheumdis-2018-214273

DOI: 10.1136/annrheumdis-2018-214273

PMC ID: 6530077

PubMed ID: 30674475

SO-VID: 7a196a67-e039-4e0e-9624-9f2c0289cde5

License:

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

History

Date received : 13 August 2018

Date revision received : 13 December 2018

Date accepted : 19 December 2018

Funding

Funded by: Novartis Pharma AG;

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ScienceOpen disciplines: Immunology

Keywords: secukinumab,inflammatory bowel disease,crohn’s disease,ulcerative colitis

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ScienceOpen disciplines: Immunology

Keywords: secukinumab, inflammatory bowel disease, crohn’s disease, ulcerative colitis

Incidence rates of inflammatory bowel disease in patients with psoriasis, psoriatic arthritis and ankylosing spondylitis treated with secukinumab: a retrospective analysis of pooled data from 21 clinical trials

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Most cited references 40

Analysis of five chronic inflammatory diseases identifies 27 new associations and highlights disease-specific patterns at shared loci

Inherited determinants of Crohn's disease and ulcerative colitis phenotypes: a genetic association study

Secukinumab is superior to ustekinumab in clearing skin of subjects with moderate to severe plaque psoriasis: CLEAR, a randomized controlled trial.

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